Displaying publications 21 - 40 of 75 in total

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  1. Beta-catenin non-canonical pathway: A potential target for inflammatory and hyperproliferative state via expression of transglutaminase 2 in psoriatic skin keratinocyte
    Gupta G, Singh Y, Tiwari J, Raizaday A, Alharbi KS, Al-Abbasi FA, et al.
    Dermatol Ther, 2020 11;33(6):e14209.
    PMID: 32816372 DOI: 10.1111/dth.14209
    Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL-23/IL-17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor-α (TNF-α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL-17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell-like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non-canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways.
    Matched MeSH terms: Keratinocytes
  2. Development of various composition multicomponent chitosan/fish collagen/glycerin 3D porous scaffolds: Effect on morphology, mechanical strength, biostability and cytocompatibility
    Ullah S, Zainol I, Chowdhury SR, Fauzi MB
    Int J Biol Macromol, 2018 May;111:158-168.
    PMID: 29305219 DOI: 10.1016/j.ijbiomac.2017.12.136
    The various composition multicomponent chitosan/fish collagen/glycerin 3D porous scaffolds were developed and investigated the effect of various composition chitosan/fish collagen/glycerin on scaffolds morphology, mechanical strength, biostability and cytocompatibility. The scaffolds were fabricated via freeze-drying technique. The effects of various compositions consisting in 3D scaffolds were investigated via FT-IR analysis, porosity, swelling and mechanical tests, and effect on the morphology of scaffolds investigated microscopically. The biostability and cytocompatibility tests were used to explore the ability of scaffolds to use for tissue engineering application. The average pore sizes of scaffolds were in range of 100.73±27.62-116.01±52.06, porosity 71.72±3.46-91.17±2.42%, tensile modulus in dry environment 1.47±0.08-0.17±0.03MPa, tensile modulus in wet environment 0.32±0.03-0.14±0.04MPa and biodegradation rate (at day 30) 60.38±0.70-83.48±0.28%. In vitro culture of human fibroblasts and keratinocytes showed that the various composition multicomponent 3D scaffolds were good cytocompatibility however, the scaffolds contained high amount of fish collagen excellently facilitated cell proliferation and adhesion. It was found that the high amount fish collagen and glycerin scaffolds have high porosity, enough mechanical strength and biostability, and excellent cytocompatibility.
    Matched MeSH terms: Keratinocytes
  3. Fulltext Counteracting the Ramifications of UVB Irradiation and Photoaging with Swietenia macrophylla King Seed
    Mahendra CK, Abidin SAZ, Htar TT, Chuah LH, Khan SU, Ming LC, et al.
    Molecules, 2021 Apr 01;26(7).
    PMID: 33916053 DOI: 10.3390/molecules26072000
    In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected. Aside from this, proteins involved in various other processes like DNA repair and maintenance, glycolysis, cell growth, proliferation, and migration were affected while the cells approached imminent cell death. Additionally, the collagen degradation pathway was also activated by UVB irradiation through the upregulation of inflammatory and collagen degrading markers. Nevertheless, with the treatment of Swietenia macrophylla (S. macrophylla) seed extract and fractions, the dysregulation of many genes and proteins by UVB was reversed. The reversal effects were particularly promising with the S. macrophylla hexane fraction (SMHF) and S. macrophylla ethyl acetate fraction (SMEAF). SMHF was able to oppose the detrimental effects of UVB in several different processes such as the redox system, DNA repair and maintenance, RNA transcription to translation, protein maintenance and synthesis, cell growth, migration and proliferation, and cell glycolysis, while SMEAF successfully suppressed markers related to skin inflammation, collagen degradation, and cell apoptosis. Thus, in summary, our research not only provided a deeper insight into the molecular changes within irradiated keratinocytes, but also serves as a model platform for future cosmetic research to build upon. Subsequently, both SMHF and SMEAF also displayed potential photoprotective properties that warrant further fractionation and in vivo clinical trials to investigate and obtain potential novel bioactive compounds against photoaging.
    Matched MeSH terms: Keratinocytes/drug effects; Keratinocytes/metabolism; Keratinocytes/radiation effects
  4. Fulltext Streptomyces sp. MUM273b: A mangrove-derived potential source for antioxidant and UVB radiation protectants
    Tan LT, Mahendra CK, Yow YY, Chan KG, Khan TM, Lee LH, et al.
    Microbiologyopen, 2019 10;8(10):e859.
    PMID: 31199601 DOI: 10.1002/mbo3.859
    Microbial natural products serve as a good source for antioxidants. The mangrove-derived Streptomyces bacteria have been evidenced to produce antioxidative compounds. This study reports the isolation of Streptomyces sp. MUM273b from mangrove soil that may serve as a promising source of antioxidants and UV-protective agents. Identification and characterization methods determine that strain MUM273b belongs to the genus Streptomyces. The MUM273b extract exhibits antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging activities and also metal-chelating activity. The MUM273b extract was also shown to inhibit the production of malondialdehyde in metal-induced lipid peroxidation. Strong correlation between the antioxidant activities and the total phenolic content of MUM273b extract was shown. In addition, MUM273b extract exhibited cytoprotective effect on the UVB-induced cell death in HaCaT keratinocytes. Gas chromatography-mass spectrometry analysis detected phenolics, pyrrole, pyrazine, ester, and cyclic dipeptides in MUM273b extract. In summary, Streptomyces MUM273b extract portrays an exciting avenue for future antioxidative drugs and cosmeceuticals development.
    Matched MeSH terms: Keratinocytes/physiology; Keratinocytes/radiation effects
  5. Fulltext Polyhexamethylene Biguanide and Nadifloxacin Self-Assembled Nanoparticles: Antimicrobial Effects against Intracellular Methicillin-Resistant Staphylococcus aureus
    Kamaruzzaman NF, Pina MF, Chivu A, Good L
    Polymers (Basel), 2018 May 12;10(5).
    PMID: 30966555 DOI: 10.3390/polym10050521
    The treatment of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge, partly due to localization of the bacteria inside the host's cells, where antimicrobial penetration and efficacy is limited. We formulated the cationic polymer polyhexamethylene biguanide (PHMB) with the topical antibiotic nadifloxacin and tested the activities against intracellular MRSA in infected keratinocytes. The PHMB/nadifloxacin nanoparticles displayed a size of 291.3 ± 89.6 nm, polydispersity index of 0.35 ± 0.04, zeta potential of +20.2 ± 4.8 mV, and drug encapsulation efficiency of 58.25 ± 3.4%. The nanoparticles killed intracellular MRSA, and relative to free polymer or drugs used separately or together, the nanoparticles displayed reduced toxicity and improved host cell recovery. Together, these findings show that PHMB/nadifloxacin nanoparticles are effective against intracellular bacteria and could be further developed for the treatment of skin and soft tissue infections.
    Matched MeSH terms: Keratinocytes
  6. ROCK2/ras(Ha) co-operation induces malignant conversion via p53 loss, elevated NF-κB and tenascin C-associated rigidity, but p21 inhibits ROCK2/NF-κB-mediated progression
    Masre SF, Rath N, Olson MF, Greenhalgh DA
    Oncogene, 2017 May 04;36(18):2529-2542.
    PMID: 27991921 DOI: 10.1038/onc.2016.402
    To study ROCK2 activation in carcinogenesis, mice expressing 4-hydroxytamoxifen (4HT)-activated ROCK2 (K14.ROCK(er)) were crossed with mice expressing epidermal-activated ras(Ha) (HK1.ras(1205)). At 8 weeks, 4HT-treated K14.ROCK(er)/HK1.ras(1205) cohorts exhibited papillomas similar to HK1.ras(1205) controls; however, K14.ROCK(er)/HK1.ras(1205) histotypes comprised a mixed papilloma/well-differentiated squamous cell carcinoma (wdSCC), exhibiting p53 loss, increased proliferation and novel NF-κB expression. By 12 weeks, K14.ROCK(er)/HK1.ras(1205) wdSCCs exhibited increased NF-κB and novel tenascin C, indicative of elevated rigidity; yet despite continued ROCK2 activities/p-Mypt1 inactivation, progression to SCC required loss of compensatory p21 expression. K14.ROCK(er)/HK1.ras(1205) papillomatogenesis also required a wound promotion stimulus, confirmed by breeding K14.ROCK(er) into promotion-insensitive HK1.ras(1276) mice, suggesting a permissive K14.ROCK(er)/HK1.ras(1205) papilloma context (wound-promoted/NF-κB(+)/p53(-)/p21(+)) preceded K14.ROCK(er)-mediated (p-Mypt1/tenascin C/rigidity) malignant conversion. Malignancy depended on ROCK(er)/p-Mypt1 expression, as cessation of 4HT treatment induced disorganized tissue architecture and p21-associated differentiation in wdSCCs; yet tenascin C retention in connective tissue extracellular matrix suggests the rigidity laid down for conversion persists. Novel papilloma outgrowths appeared expressing intense, basal layer p21 that confined endogenous ROCK2/p-Mypt1/NF-κB to supra-basal layers, and was paralleled by restored basal layer p53. In later SCCs, 4HT cessation became irrelevant as endogenous ROCK2 expression increased, driving progression via p21 loss, elevated NF-κB expression and tenascin C-associated rigidity, with p-Mypt1 inactivation/actinomyosin-mediated contractility to facilitate invasion. However, p21-associated inhibition of early-stage malignant progression and the intense expression in papilloma outgrowths, identifies a novel, significant antagonism between p21 and ras(Ha)/ROCK2/NF-κB signalling in skin carcinogenesis. Collectively, these data show that ROCK2 activation induces malignancy in ras(Ha)-initiated/promoted papillomas in the context of p53 loss and novel NF-κB expression, whereas increased tissue rigidity and cell motility/contractility help mediate tumour progression.
    Matched MeSH terms: Keratinocytes/pathology; Keratinocytes/virology
  7. In vitro biocompatibility of chitosan porous skin regenerating templates (PSRTs) using primary human skin keratinocytes
    Lim CK, Yaacob NS, Ismail Z, Halim AS
    Toxicol In Vitro, 2010 Apr;24(3):721-7.
    PMID: 20079826 DOI: 10.1016/j.tiv.2010.01.006
    Biopolymer chitosan (beta-1,4-d-glucosamine) comprises the copolymer mixture of N-acetylglucosamine and glucosamine. The natural biocompatibility and biodegradability of chitosan have recently highlighted its potential use for applications in wound management. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability, but it is unknown as to what degree. Hence, the biocompatibility of the chitosan porous skin regenerating templates (PSRT 82, 87 and 108) was determined using an in vitro toxicology model at the cellular and molecular level on primary normal human epidermal keratinocytes (pNHEK). Cytocompatibility was accessed by using a 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assay from 24 to 72h. To assess the genotoxicity of the PSRTs, DNA damage to the pNHEK was evaluated by using the Comet assay following direct contact with the various PSRTs. Furthermore, the skin pro-inflammatory cytokines TNF-alpha and IL-8 were examined to evaluate the tendency of the PSRTs to provoke inflammatory responses. All PSRTs were found to be cytocompatible, but only PSRT 108 was capable of stimulating cell proliferation. While all of the PSRTs showed some DNA damage, PSRT 108 showed the least DNA damage followed by PSRT 87 and 82. PSRT 87 and 82 induced a higher secretion of TNF-alpha and IL-8 in the pNHEK cultures than did PSRT 108. Hence, based on our experiments, PSRT 108 is the most biocompatible wound dressing of the three tested.
    Matched MeSH terms: Keratinocytes/drug effects*
  8. Cultured epidermal autografts in combination with MEEK Micrografting technique in the treatment of major burn injuries
    Dorai AA, Lim CK, Fareha AC, Halim AS
    Med J Malaysia, 2008 Jul;63 Suppl A:44.
    PMID: 19024976
    The treatment of major burn injuries are a formidable challenge to the burn surgeon. Early aggressive surgery for deep to full thickness burn injuries is vital in the prevention of infection. The ultimate goal in major burn injuries is to prevent the onset of multi-resistant organisms and achieve early wound cover. The field of tissue engineering can help to expedite the healing of these burn wounds. The development of keratinocyte culture delivery system can be used clinically to fasten the healing process and save many lives.
    Matched MeSH terms: Keratinocytes/cytology*
  9. Immunohistochemical expression of Tazarotene-induced Gene 3 in oral squamous cell carcinoma
    Venkataswamy P, Samudrala Venkatesiah S, Rao RS, Banavar SR, Patil S, Augustine D, et al.
    J Oral Pathol Med, 2020 Dec 01.
    PMID: 33259689 DOI: 10.1111/jop.13144
    BACKGROUND: The prognosis of hyperproliferative skin lesions, such as psoriasis, basal cell carcinoma, and non-melanoma skin cancers, is significantly benefited from the levels of tazarotene-induced gene-1 (TIG3) expression and subsequent treatment with tazarotene. Such observations suggest that TIG3 could be used as a biomarker for apoptosis, differentiation, and proliferation. The current study aimed to evaluate the expression of TIG3 in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) compared with normal skin (NS) and skin squamous cell carcinoma (SSCC) using immunohistochemistry.

    METHODS: Seventeen cases each of SSCC, OSCC, NOM, and NS were evaluated. Each section was immunohistochemically stained with a rabbit polyclonal TIG3 antibody. The entire procedure was blinded and evaluated by 5 observers. Statistical analysis was performed using the chi-square test.

    RESULTS: There was a significant decrease in TIG3 protein expression in OSCC and SSCC compared with that in NOM and NS (P = 0.008). The progressive loss of expression was observed as the grade of both malignancies increased. However, there was no significant difference in the expression among the normal tissue groups and within SCC groups of similar grades.

    CONCLUSION: The present study suggests that the loss of TIG3 is an important event in carcinogenesis. TIG3 acts as a regulator of keratinocyte proliferation and terminal differentiation. Therefore, TIG3 could be a potential biomarker to differentiate aggressive and non-aggressive neoplasms.

    Matched MeSH terms: Keratinocytes
  10. In vitro cytotoxicology model of oligo-chitosan and n, o-carboxymethyl chitosan using primary normal human epidermal keratinocyte cultures
    Lim CK, Halim AS, Lau HY, Ujang Z, Hazri A
    J Appl Biomater Biomech, 2007 May-Aug;5(2):82-7.
    PMID: 20799177
    Chitosan (beta-1, 4-D-glucosamine) is a deacetylated form of chitin with excellent biological properties in wound management. The natural properties of chitosan have the physical and chemical limitations to be widely used in biomedical fields. The improvement of the physical and chemical properties of chitosan with some additional chemicals will alter its biocompatibility. Therefore, the biological attribute of the modified chitosan must be evaluated. In this study, the cytotoxicity of oligo-chitosan (OC) and N, O- carboxymethyl-chitosan (NO-CMC) derivatives (O-C 1%, O-C 5%, NO-CMC 1% and NO-CMC 5%) was evaluated using primary normal human epidermal keratinocyte (pNHEK) cultures as an in vitro toxicology model at standardized cell passages (fourth passages). 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl tetrazolium bromide (MTT) was used as a cell viability assay. The O-C 1% is one of the most compatible chitosan derivatives because it steadily sustained >70% of viable cells until 72 hr post-treatment. This was followed by O-C 5%, NO-CMC 5% and NO-CMC 1%. Therefore, oligo-chitosan had the ideal properties of a biocompatible material compared to N, O- carboxymethyl-chitosan in this study.
    Matched MeSH terms: Keratinocytes
  11. Fulltext In vivo response of GsdmA3(Dfl)/+ mice to topically applied fish oil - effects on cellular markers and macrophages
    Zulfakar MH, Porter RM, Heard CM
    FEBS Open Bio, 2016 08;6(8):827-34.
    PMID: 27516961 DOI: 10.1002/2211-5463.12095
    Psoriasis is an incurable autoimmune disease characterized by patches of abnormal red, itchy and scaly skin. This work examined the modulation of inflammation, hyperproliferation and immune cell markers following topical application of fish oil (FO) in comparison to the antipsoriatic agents, betamethasone dipropionate (BD) and salicylic acid (SA), to GsdmA3(Dfl)/+ mice, a hair loss mutant which also exhibits epidermal hyperproliferation akin to psoriasis. The mice were dosed with 100 mg of the test formulation and after 10 days, the mice were sacrificed, skin sections excised and subjected to immunohistochemical determination of COX-2, K17 and MAC-1; and immunofluorescence of Ki-67. Unchanged expression of the proinflammatory enzyme COX-2 was observed in all treatments, suggesting the noninvolvement of COX-2 in the aetiology of cutaneous aberration seen in GsdmA3(Dfl)/+ mice. Intense staining of K17 and MAC-1 in the FO-treated group mirrored the epidermal thickening seen observed in live mice by optical coherence tomography (OCT). The ratio of Ki-67-positive nuclei per 100 basal cells indicated that hyperproliferation of keratinocytes occurred in FO-treated mice and the opposite was true for BD-treated mice. There was a positive correlation (R (2) 0.995) between Ki-67 and the epidermal thickness data observed previously. In all immunochemical procedures, the combined BD, SA and FO formulation did not show any significant difference with the control group, reflecting observations seen previously. In conclusion, the epidermal changes observed following topical FO treatment on GsdmA3(Dfl)/+ mice involves an increase in cellular proliferation and macrophages, although COX-2 does not appear to play an important role.
    Matched MeSH terms: Keratinocytes
  12. Fulltext Isolation and enhancement of a homogenous in vitro human Hertwig's epithelial root sheath cell population
    Farea M, Halim AS, Abdullah NA, Lim CK, Mokhtar KI, Berahim Z, et al.
    Int J Mol Sci, 2013;14(6):11157-70.
    PMID: 23712356 DOI: 10.3390/ijms140611157
    Hertwig's epithelial root sheath (HERS) cells play a pivotal role during root formation of the tooth and are able to form cementum-like tissue. The aim of the present study was to establish a HERS cell line for molecular and biochemical studies using a selective digestion method. Selective digestion was performed by the application of trypsin-EDTA for 2 min, which led to the detachment of fibroblast-like-cells, with the rounded cells attached to the culture plate. The HERS cells displayed a typical cuboidal/squamous-shaped appearance. Characterization of the HERS cells using immunofluorescence staining and flow cytometry analysis showed that these cells expressed pan-cytokeratin, E-cadherin, and p63 as epithelial markers. Moreover, RT-PCR confirmed that these cells expressed epithelial-related genes, such as cytokeratin 14, E-cadherin, and ΔNp63. Additionally, HERS cells showed low expression of CD44 and CD105 with absence of CD34 and amelogenin expressions. In conclusion, HERS cells have been successfully isolated using a selective digestion method, thus enabling future studies on the roles of these cells in the formation of cementum-like tissue in vitro.
    Matched MeSH terms: Keratinocytes/cytology; Keratinocytes/metabolism
  13. Concentration-dependent effect of platelet-rich plasma on keratinocyte and fibroblast wound healing
    Xian LJ, Chowdhury SR, Bin Saim A, Idrus RB
    Cytotherapy, 2015 Mar;17(3):293-300.
    PMID: 25456581 DOI: 10.1016/j.jcyt.2014.10.005
    Platelet-rich plasma (PRP) has been found to contain a high concentration of growth factors that are present during the process of healing. Studies conducted found that application of PRP accelerates wound healing. In this study, we characterized the skin cell suspension harvested using the co-isolation technique and evaluated the effects of PRP (10% and 20%, v/v) on co-cultured keratinocytes and fibroblasts in terms of wound healing.
    Matched MeSH terms: Keratinocytes/physiology*
  14. Platelet-rich plasma with keratinocytes and fibroblasts enhance healing of full-thickness wounds
    Law JX, Chowdhury SR, Saim AB, Idrus RBH
    J Tissue Viability, 2017 Aug;26(3):208-215.
    PMID: 28615133 DOI: 10.1016/j.jtv.2017.05.003
    Advances in tissue engineering led to the development of various tissue-engineered skin substitutes (TESS) for the treatment of skin injuries. The majority of the autologous TESS required lengthy and costly cell expansion process to fabricate. In this study, we determine the possibility of using a low density of human skin cells suspended in platelet-rich plasma (PRP)-enriched medium to promote the healing of full-thickness skin wounds. To achieve this, full-thickness wounds of size 1.767 cm2 were created at the dorsum part of nude mice and treated with keratinocytes (2 × 104 cells/cm2) and fibroblasts (3 × 104 cells/cm2) suspended in 10% PRP-enriched medium. Wound examination was conducted weekly and the animals were euthanized after 2 weeks. Gross examination showed that re-epithelialization was fastest in the PRP+cells group at both day 7 and 14, followed by the PRP group and NT group receiving no treatment. Only the PRP+cells group achieved complete wound closure by 2 weeks. Epidermal layer was presence in the central region of the wound of the PRP+cells and PRP groups but absence in the NT group. Comparison between the PRP+cells and PRP groups showed that the PRP+cells-treated wound was more mature as indicated by the presence of thinner epidermis with single cell layer thick basal keratinocytes and less cellular dermis. In summary, the combination of low cell density and diluted PRP creates a synergistic effect which expedites the healing of full-thickness wounds. This combination has the potential to be developed as a rapid wound therapy via the direct application of freshly harvested skin cells in diluted PRP.
    Matched MeSH terms: Keratinocytes/pathology; Keratinocytes/physiology
  15. In Vitro and In Vivo Skin Distribution of 5α-Reductase Inhibitors Loaded Into Liquid Crystalline Nanoparticles
    Madheswaran T, Baskaran R, Yoo BK, Kesharwani P
    J Pharm Sci, 2017 11;106(11):3385-3394.
    PMID: 28652158 DOI: 10.1016/j.xphs.2017.06.016
    In this study, we developed positively charged liquid crystalline nanoparticles (LCN) coated with chitosan (CHI) to enhance the skin permeation and distribution of 5α-reductase inhibitors for the treatment of androgenetic alopecia. LCN and surface-modified LCN (CHI-LCN) were prepared by ultrasonication method, and their physicochemical properties were characterized. In vitro and in vivo skin permeation and retention were studied using porcine abdominal skin and mice skin using the Franz diffusion cell. Skin distribution and cellular uptake of LCN and CHI-LCN were also investigated. The particle size and surface charge were 244.9 ± 2.1 nm and -19.2 ± 1.1 mV, respectively, for LCNs and 300.0 ± 7.6 nm and 24.7 ± 2.4 mV, respectively, for CHI-LCN. The permeation of 5α-reductase inhibitors was significantly greater with CHI-LCN compared with LCN, whereas there was no significant difference observed in the skin distribution. In fluorescence studies, fluorescence intensity was higher for CHI-LCNs throughout the skin, whereas more intense fluorescence was seen only in the epidermis layer for LCN. CHI-LCN showed greater cellular uptake than LCN, resulting in internalization of 98.5 ± 1.9% of nanoparticles into human keratinocyte cells. In conclusion, surface modification of LCN with CHI is a promising strategy for increasing skin permeation of 5α-reductase inhibitors for topical delivery.
    Matched MeSH terms: Keratinocytes/metabolism
  16. Fulltext Gut Bacteria of Rattus rattus (Rat) Produce Broad-Spectrum Antibacterial Lipopeptides
    Akbar N, Siddiqui R, Iqbal M, Sagathevan K, Kim KS, Habib F, et al.
    ACS Omega, 2021 May 11;6(18):12261-12273.
    PMID: 34056379 DOI: 10.1021/acsomega.1c01137
    Among several animals, Rattus rattus (rat) lives in polluted environments and feeds on organic waste/small invertebrates, suggesting the presence of inherent mechanisms to thwart infections. In this study, we isolated gut bacteria of rats for their antibacterial activities. Using antibacterial assays, the findings showed that the conditioned media from selected bacteria exhibited bactericidal activities against Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, and Salmonella enterica) and Gram-positive (Bacillus cereus, methicillin-resistant Staphylococcus aureus, and Streptococcus pyogenes) pathogenic bacteria. The conditioned media retained their antibacterial properties upon heat treatment at boiling temperature for 10 min. Using MTT assays, the conditioned media showed minimal cytotoxic effects against human keratinocyte cells. Active conditioned media were subjected to tandem mass spectrometry, and the results showed that conditioned media from Bacillus subtilis produced a large repertoire of surfactin and iturin A (lipopeptides) molecules. To our knowledge, this is the first report of isolation of lipopeptides from bacteria isolated from the rat gut. In short, these findings are important and provide a platform to develop effective antibacterial drugs.
    Matched MeSH terms: Keratinocytes
  17. Fulltext Cyclodextrin inclusion complex inhibits circulating galectin-3 and FGF-7 and affects the reproductive integrity and mobility of Caco-2 cells
    Maki MAA, Cheah SC, Bayazeid O, Kumar PV
    Sci Rep, 2020 10 15;10(1):17468.
    PMID: 33060727 DOI: 10.1038/s41598-020-74467-1
    Galectin-3 (Gal-3) is a carbohydrate-binding protein, that promotes angiogenesis through mediating angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). There is strong evidence confirming FGF involvement in tumor growth and progression by disrupting cell proliferation and angiogenesis. In this study, we investigated the effect of β-cyclodextrin:everolimus:FGF-7 inclusion complex (Complex) on Caco-2 cell migration, cell motility and colony formation. In addition, we examined the inhibitory effect of the Complex on the circulating proteins; Gal-3 and FGF-7. Swiss Target Prediction concluded that Gal-3 and FGF are possible targets for β-CD. Results of the chemotaxis cell migration assay on Caco-2 cell line revealed that the Complex has higher reduction in cell migration (78.3%) compared to everolimus (EV) alone (58.4%) which is possibly due to the synergistic effect of these molecules when used as a combined treatment. Moreover, the Complex significantly decreased the cell motility in cell scratch assay, less than 10% recovery compared to the control which has ~ 45% recovery. The Complex inhibited colony formation by ~ 75% compared to the control. Moreover, the Complex has the ability to inhibit Gal-3 with minimum inhibitory concentration of 33.46 and 41 for β-CD and EV, respectively. Additionally, β-CD and β-CD:EV were able to bind to FGF-7 and decreased the level of FGF-7 more than 80% in cell supernatant. This confirms Swiss Target Prediction result that predicted β-CD could target FGF. These findings advance the understanding of the biological effects of the Complex which reduced cell migration, cell motility and colony formation and it is possibly due to inhibiting circulating proteins such as; Gal-3 and FGF-7.
    Matched MeSH terms: Keratinocytes/cytology
  18. Fulltext The Role of Calcium in Wound Healing
    Subramaniam T, Fauzi MB, Lokanathan Y, Law JX
    Int J Mol Sci, 2021 Jun 17;22(12).
    PMID: 34204292 DOI: 10.3390/ijms22126486
    Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.
    Matched MeSH terms: Keratinocytes/metabolism
  19. Synergistic antibacterial actions of graphene oxide and antibiotics towards bacteria and the toxicological effects of graphene oxide on human epidermal keratinocytes
    Pulingam T, Thong KL, Appaturi JN, Nordin NI, Dinshaw IJ, Lai CW, et al.
    Eur J Pharm Sci, 2020 Jan 15;142:105087.
    PMID: 31626968 DOI: 10.1016/j.ejps.2019.105087
    Graphene oxide (GO) has displayed antibacterial activity that has been investigated in the past, however, information on synergistic activity of GO with conventional antibiotics is still lacking. The objectives of the study were to determine the combinatorial actions of GO and antibiotics against Gram-positive and Gram-negative bacteria and the toxicological effects of GO towards human epidermal keratinocytes (HaCaT). Interactions at molecular level between GO and antibiotics were analyzed using Attenuated Total Reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR). Changes in the antibacterial activity of antibiotics towards bacteria through the addition of GO was investigated. Toxicity of GO towards HaCaT cells were examined as skin cells play a role as the first line of defense of the human body. The ATR-FTIR characterizations of GO and antibiotics showed adsorption of tested antibiotics onto GO. The combinatorial antibacterial activity of GO and antibiotics were found to increase when compared to GO or antibiotic alone. This was attributed to the ability of GO to disrupt bacterial membrane to allow for better adsorption of antibiotics. Cytotoxicity of GO was found to be dose-dependent towards HaCaT cell line, it is found to impose negligible toxic effects against the skin cells at concentration below 100 μg/mL.
    Matched MeSH terms: Keratinocytes/drug effects*; Keratinocytes/metabolism
  20. An Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles for Transdermal Delivery
    Nair RS, Morris A, Billa N, Leong CO
    AAPS PharmSciTech, 2019 Jan 10;20(2):69.
    PMID: 30631984 DOI: 10.1208/s12249-018-1279-6
    Curcumin-loaded chitosan nanoparticles were synthesised and evaluated in vitro for enhanced transdermal delivery. Zetasizer® characterisation of three different formulations of curcumin nanoparticles (Cu-NPs) showed the size ranged from 167.3 ± 3.8 nm to 251.5 ± 5.8 nm, the polydispersity index (PDI) values were between 0.26 and 0.46 and the zeta potential values were positive (+ 18.1 to + 20.2 mV). Scanning electron microscopy (SEM) images supported this size data and confirmed the spherical shape of the nanoparticles. All the formulations showed excellent entrapment efficiency above 80%. FTIR results demonstrate the interaction between chitosan and sodium tripolyphosphate (TPP) and confirm the presence of curcumin in the nanoparticle. Differential scanning calorimetry (DSC) studies of Cu-NPs indicate the presence of curcumin in a disordered crystalline or amorphous state, suggesting the interaction between the drug and the polymer. Drug release studies showed an improved drug release at pH 5.0 than in pH 7.4 and followed a zero order kinetics. The in vitro permeation studies through Strat-M® membrane demonstrated an enhanced permeation of Cu-NPs compared to aqueous curcumin solution (p ˂ 0.05) having a flux of 0.54 ± 0.03 μg cm-2 h-1 and 0.44 ± 0.03 μg cm-2 h-1 corresponding to formulations 5:1 and 3:1, respectively. The cytotoxicity assay on human keratinocyte (HaCat) cells showed enhanced percentage cell viability of Cu-NPs compared to curcumin solution. Cu-NPs developed in this study exhibit superior drug release and enhanced transdermal permeation of curcumin and superior percentage cell viability. Further ex vivo and in vivo evaluations will be conducted to support these findings.
    Matched MeSH terms: Keratinocytes/drug effects
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