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  1. Mohd Hafiz Arzmi
    MyJurnal
    A balanced oral microbiome is essential in maintaining a healthy oral cavity. Oral microbiome comprises of var-ious microorganisms that belong to different kingdoms, including bacteria (bacteriome) and fungal (mycobiome). Multiple factors have been shown in oral carcinogenesis including alcohol consumption, tobacco smoking, betel nut chewing and microbial infections. Since the oral cavity comprises of various microbial kingdoms, thus, in-ter-kingdom interactions are suggested in promoting oral carcinogenesis. Dysbiosis, which is defined as imbalance inter-kingdom microbiome, alone may not cause oral carcinogenesis; thus, it is suggested that nutritional factor may also play a vital role in this disease development. A recent study has shown that sucrose consumption can induce the production of glucosyltransferases (gtfs) by Streptococcus mutans which lead to the increasing attachment of Candida albicans in polymicrobial biofilms form. The yeast has been reported to be potentially involved in oral carcinogenesis, particularly in the immunocompromised patient. This is due to the inflammation that is caused by candidal infection, which increases pro-inflammatory cytokines such as interleukin-6, interleukin-8 and interleu-kin-10, that have been linked to oral carcinogenesis. However, further study is needed to conform to the claim. In addition, over-consumption of alcoholic beverages has also been related to carcinogenesis which the ethanol has been reported to be converted into acetaldehyde by C. albicans using acetaldehyde dehydrogenases enzymes. In Malaysia, oral cancer has also been related to the consumption of cured and salted fish, which mostly consumed by the Chinese ethnics. However, its relationship to oral microbiome remains unclear. In conclusion, oral microbiome and nutrition may have a role in oral carcinogenesis; however, further study is needed to elucidate the role of both factors in oral cancer development.
  2. Noor Afifah Hanin Mohamad, Mohd Hafiz Arzmi, Noratikah Othman
    IIUM Medical Journal Malaysia, 2019;18(102):62-0.
    MyJurnal
    Actinomyces naeslundii is an oral microbiome that has been suggested to involve in actinomycosis particularly in immunocompromised patients. However, studies have also shown that the bacterium can inhibit the colonisation of Candida albicans and cariogenic bacterium, Streptococcus mutans. Even though various studies have been conducted to characterise A. naeslundii, however, the role of the bacterium in the oral cavity either to induce pathogenicity or to improve oral health remain unclear. The objective of this study is to determine the role of A. naeslundii in the oral cavity using bioinformatic tools with the hypothesis that A. naeslundii possesses genome similarity to oral probiotics. Materials and method: The study was conducted by data mining of the genomic sequences of A. naeslundii NCTC10301 from GenBank. Following that, genomic comparison was performed with 25 species of well-known probiotics. MAUVE version 2.3.1 was used to find similarities between A. naeslundii with the known probiotics through identification of potential relevance probiotic properties in A. naeslundii. Phylogenetic tree was constructed using PHYLIP package to identify evolutionary relationship of A. naeslundii with the known probiotics. The 16s rRNA sequences of A. naeslundii and known probiotics were harvested from GenBank using BLAST. Finally, the functions of all A. naeslundii genes that shared similarity with known probiotics were identified using INTERPRO. Result: Genome comparison analysis of the present study showed that A. naeslundii genome exhibited high similarity to Bifidobacterium species such as B. animalis subsp. lactis, B. bifidum, B. longum and B. breve. In addition, phylogenetic tree analysis showed that Bacillus species, B. subtilis and B. cereus , appeared to clade together with A. naeslundii, with bootstrap value of 98%. Conclusion: A. naeslundii had high similarity with probiotic Bifidobacterium species thus supported the hypothesis of the present study that A. naeslundii possesses genome similarity to oral probiotic.
  3. Muhammad Lutfi Mohamed Halim, Nora Azirah Mohd Zayi, Mohd Yusof Mohamad, Mohd Hafiz Arzmi
    MyJurnal
    Introduction: Oral cancer is the sixth most common malignancy in the world. It is a major concern in Southeast Asia primarily due to betel quid chewing, smoking, and alcohol consumption. In Malaysia, oral cancer related cases accounts for 1.55% of the cause of deaths. Despite recent advances in cancer diagnoses and therapies, the survival rate of oral cancer patients only reached 50% in the last few decades. Tissue engineering (TE) principles may pro-vide new technology platforms to study mechanisms of angiogenesis and tumour cell growth as well as potentially tumour cell spreading in cancer research. The use of biomaterial, appropriate cell source and proper signalling mol-ecules are vital components of TE. Collagen biomaterial are widely used scaffold or membrane in oral application. Nevertheless, no review has been performed on the its usage for the study of oral cancer. This study aimed to sys-tematically review the use of collagen scaffold in oral cancer application. Methods: Research articles were searched using Scopus, Pubmed and Web of Science (WOS) databases. The keywords were limited to “collagen membrane OR collagen scaffold” AND “oral cancer”. Results: Initial search yielded 61 papers (Scopus:37, Pubmed: 12, WOS: 12). Further scrutinization of the papers based on the inclusion criteria resulted total of 3 papers. Two of the papers used collagen membrane for regeneration of oral mucosal defect and increment of alveolar ridge height post-surgery. The remaining paper utilize collagen biomaterial as scaffold for the culture of adenoid cystic carcinoma (ACC) cells. All papers reported significant role of collagen biomaterial in terms of tissue formation, healing scaffold and cellular proliferation. Conclusion: Collagen utilization as biomaterial offers potential use for regeneration of oral related structures as well providing useful model for therapeutics anti-cancer research.
  4. Nurul Alia Risma Rismayuddin, Munirah Mokhtar, Noratikah Othman, Ahmad Faisal Ismail, Mohd Hafiz Arzmi
    MyJurnal
    Introduction:Candida albicans is an opportunistic fungus that is associated with oral carcinogenesis. In addition, biofilm formation has been one of the important virulence factors of the yeast. Streptococcus salivarius K12 is an oral probiotic while Musa acuminata is a well-known prebiotic. The objective of this study is to investigate the effect of S. salivarius K12 and M. acuminata skin aqueous extract (synbiotic) on C. albicans with the hypothesis that S. salivariusK12 and M. acuminata inhibit C. albicans biofilm formation. Methods: To develop mono-species biofilm, C. albicans(ATCC MYA-4901 and cancer isolates, ALC2 and ALC3 strains) and S. salivarius K12 were standardised to 105 cells and 106 cells, respectively and grown in 96-well plate in nutrient broth (NB) or RPMI at 37 °C for 72 h. Polymicro-bial biofilms were developed by inoculating both microorganisms in the same well with similar cell number as in mono-species. To determine the effect of synbiotic, similar protocol was repeated by mixing with 800 mg mL-1 of M. acuminata skin extract and incubated at 37 °C for 72 h. The medium was replenished at every 24 h, aseptically. Finally, the biofilms were assessed using crystal violet assay and the optical density was measured at OD620nm. Results:C. albicans strain MYA-4901 and ALC3, when grown in polymicrobial with S. salivarius K12 in NB that is predominated by yeast-form C. albicans, exhibited decreased biofilms by 71.40±11.7% and 49.40±3.9%, respec-tively when compared to the expected biofilms. Meanwhile in RPMI, which C. albicans strain ATCC MYA-4901, ALC2 and ALC3 were predominated by hyphal-form showed decreased biofilms by 72.0±26.7%, 53.4±14.4% and 65.7±6.7%, respectively when compared to the expected biofilms. Conclusion:S. salivarius K12 and M. acuminata skin extract synbiotic inhibit biofilm formation of C. albicans yeast and hyphal forms thus supported the hypothesis of the present study.
  5. Sharmeen Nellisa Soffian, Nurul Alia Risma Rismayuddin, Munirah Mokhtar, Mohd Hafiz Arzmi
    MyJurnal
    Introduction:Candida spp. are most common opportunistic pathogenic yeast that inhabit human oral cavity, epider-mis, gastrointestinal tract, and vagina leading to candidiasis. The transition of this yeast from commensal to potent pathogen is facilitated by numbers of virulence factors including biofilm formation. While most reports on candidi-asis are associated with formation Candida albicans biofilms, however, non-albicans Candida species prevalence is of growing concern. Recently, the use of probiotics as antifungal and antibiofilm has gained an increasing attention. As such, we aim to evaluate the inhibitory effect of monomicrobial and polymicrobial of Streptococcus salivariuson six strains of NAC namely Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitanaei, Candida parapsilosis and Candida tropicalis. Methods: Antifungal activity of S. salivarius on NAC species was performed using well diffusion method on Mueller Hinton Agar (MHA) and the diameter of inhibition zone were assessed. For formation of monomicrobial biofilm, standardized cell suspensions of NAC species (1 x 105 cells/ml) and probiotic Streptococcus salivarius (1 x 106 cells/ml) were grown in RPMI or nutrient broth media at 37°C for 72 h. Meanwhile to study polymicrobial biofilm of both NAC and S. salivarius, similar protocol was employed by inoculating both microorganisms with a similar cell density as in monomicrobial. Finally, biofilm formation was assessed through quantification of total biomass by crystal violet (CV) assay and the absorbance of adherent biofilm was measured in triplicate at 620nm. Results: Antifungal susceptibility testing of S. salivarius on all six NAC species discerned no zone of inhibition. Furthermore, our results showed variability of monomicrobial and polymicrobial biofilm biomass between NAC species and growth medium. All six polymicrobial NB-grown and RPMI-grown exhibited decreased of the biofilm formation. C. parapsilosis co-cultured with S. salivarius in NB medium had shown lowest biofilm bio-mass by 75.51+_1.34% while in RPMI medium, C. lusitanaei demonstrated with most reduced biofilm biomass by 67.03+_5.19. Conclusion: Our study elucidated the antagonistic relationship between Streptococcus salivarius and non-albicans Candida by supressing the growth of polymicrobial biofilm and pseudohyphae/hyphae of NAC species.
  6. Munirah Mokhtar, RidhwanAbdul Wahab, Muhamad Ashraf Rostam, Alia Risma Rismayuddin, Mohd Hamzah Mohd Nasir, Mohd Hafiz Arzmi
    IIUM Medical Journal Malaysia, 2019;18(102):67-0.
    MyJurnal
    Oral cancer is the sixth most common cancer worldwide with Candida albicans infection being one of the aetiological factors for the disease. Meanwhile, Streptococcus salivarius K12 is an oral probiotic that is beneficial to the oral cavity. The objective of the present study is to determine the effect of S. salivarius K12 on C. albicans biofilm-forming ability with the hypothesis that S. salivarius K12 inhibits biofilm formation of C. albicans Materials and method: To assess the effect of S. salivarius K12 on C. albicans biofilm formation, S. salivarius K12, lab strain C. albicans MYA-4901 and clinical isolates from oral cancer, ALC2 and ALC3 were grown in both nutrient broth (NB) and RPMI. In a mono-species biofilm, 105 of C. albicans cells and 106 of S. salivarius K12 cells were grown separately in a 96-well plate. In contrast, both microorganisms were combined for polymicrobial biofilms with similar cell numbers as in mono-species. The biofilms were incubated for 72 hours at 37°C and the media were replenished every 24 hours. Finally, the crystal violet assay was conducted, and the optical density was measured at OD620nm. Results: Polymicrobial biofilms of C. albicans (MYA-4901 and ALC3) with S. salivarius K12 when grown in NB, exhibited a decrease by 64.5 ± 25.8% and 83.7 ± 5.4%, respectively when compared to the expected biofilms which were predominated by yeast form. Furthermore, polymicrobial biofilms of C. albicans (ALC2 and ALC3) with S. salivarius K12 showed a decrease by 62.5 ± 25.6% and 55.9 ± 17.1 %, respectively when compared to the expected biofilms when grown in RPMI that were predominated by hyphal form. Conclusion: S. salivarius K12 inhibited polymicrobial biofilms formation of C. albicans yeast and hyphal forms, thus supported the hypothesis that S. salivarius K12 inhibits biofilm formation of C. albicans.
  7. Wan Nur Fatihah Wan Mohd Kamaluddin, Ahmad Faisal Ismail, Edre Mohamad Aidid, Noratikah Othman, Mohd Hafiz Arzmi
    IIUM Medical Journal Malaysia, 2019;18(102):58-0.
    MyJurnal
    The prevalence of oral cancer has been reported annually along with high mortality rate. Probiotics have been suggested to possess anti-cancer properties, however the role of these microorganisms on oral cancer is remain unclear. The objective of the present study is to identify the mechanisms exerted by probiotics on oral carcinogenesis by using systematic review and meta analysis with the hypothesis that probiotics inhibit oral carcinogenesis. Materials and method: Comprehensive literature search was conducted on PubMed, Scopus and Web of Science electronic database from January 2019 until April 2019. Main keywords that were used are “probiotic” AND “oral cancer”. Articles that were published in English language were included in this review. Articles were selected independently by three authors and inspected independently by another researcher. The titles and abstracts of the studies were screened to identify studies that meet the inclusion criteria. Full text articles of the remaining studies were assessed to determine the availability to be included in the review. Meta-analysis was conducted by using RevMan 5 software, and the result was graphically plotted on the forest plot. This review was done according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA-P) 2015 guidelines. Results: After thorough screening of the full text articles, seven papers were eligible to be included in the systematic review. The included articles were mainly discussed on the association of probiotics and oral cancer. Two from the seven papers were selected to be analyse for quantitative synthesis (meta-analysis). The present study also showed that, Lactobacillus salivarius REN produces protective effect from developing neoplastic tongue lesions with odd ratio < 1. Conclusion: Probiotics were found to confer positive effect as an inhibitory agent against the oral carcinogenesis thus supported the hypothesis of the present study that probiotics can inhibit oral carcinogenesis.
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