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Fulltext Maximizing Postoperative Recovery: The Role of Functional Biomaterials as Nasal Packs-A Comprehensive Systematic Review without Meta-Analysis (SWiM)

Razali RA, Vijakumaran U, Fauzi MB, Lokanathan Y

Pharmaceutics, 2023 May 18;15(5).
PMID: 37242776 DOI: 10.3390/pharmaceutics15051534

Numerous biomaterials have been developed over the years to enhance the outcomes of endoscopic sinus surgery (ESS) for patients with chronic rhinosinusitis. These products are specifically designed to prevent postoperative bleeding, optimize wound healing, and reduce inflammation. However, there is no singular material on the market that can be deemed the optimal material for the nasal pack. We systematically reviewed the available evidence to assess the functional biomaterial efficacy after ESS in prospective studies. The search was performed using predetermined inclusion and exclusion criteria, and 31 articles were identified in PubMed, Scopus, and Web of Science. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess each study's risk of bias. The studies were critically analyzed and categorized into types of biomaterial and functional properties, according to synthesis without meta-analysis (SWiM) guidelines. Despite the heterogeneity between studies, it was observed that chitosan, gelatin, hyaluronic acid, and starch-derived materials exhibit better endoscopic scores and significant potential for use in nasal packing. The published data support the idea that applying a nasal pack after ESS improves wound healing and patient-reported outcomes.
Fulltext Is There an Interconnection between Epithelial-Mesenchymal Transition (EMT) and Telomere Shortening in Aging?

Imran SAM, Yazid MD, Idrus RBH, Maarof M, Nordin A, Razali RA, et al.

Int J Mol Sci, 2021 Apr 09;22(8).
PMID: 33918710 DOI: 10.3390/ijms22083888

Epithelial-Mesenchymal Transition (EMT) was first discovered during the transition of cells from the primitive streak during embryogenesis in chicks. It was later discovered that EMT holds greater potential in areas other than the early development of cells and tissues since it also plays a vital role in wound healing and cancer development. EMT can be classified into three types based on physiological functions. EMT type 3, which involves neoplastic development and metastasis, has been the most thoroughly explored. As EMT is often found in cancer stem cells, most research has focused on its association with other factors involving cancer progression, including telomeres. However, as telomeres are also mainly involved in aging, any possible interaction between the two would be worth noting, especially as telomere dysfunction also contributes to cancer and other age-related diseases. Ascertaining the balance between degeneration and cancer development is crucial in cell biology, in which telomeres function as a key regulator between the two extremes. The essential roles that EMT and telomere protection have in aging reveal a potential mutual interaction that has not yet been explored, and which could be used in disease therapy. In this review, the known functions of EMT and telomeres in aging are discussed and their potential interaction in age-related diseases is highlighted.
Fulltext Approaches in Hydroxytyrosol Supplementation on Epithelial-Mesenchymal Transition in TGFβ1-Induced Human Respiratory Epithelial Cells

Razali RA, Yazid MD, Saim A, Idrus RBH, Lokanathan Y

Int J Mol Sci, 2023 Feb 16;24(4).
PMID: 36835384 DOI: 10.3390/ijms24043974

Hydroxytyrosol (HT) is an olive polyphenol with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of HT treatment on epithelial-mesenchymal transition (EMT) in primary human respiratory epithelial cells (RECs) isolated from human nasal turbinate. HT dose-response study and growth kinetic study on RECs was performed. Several approaches on HT treatment and TGFβ1 induction with varying durations and methods was studied. RECs morphology and migration ability were evaluated. Vimentin and E-cadherin immunofluorescence staining and Western blotting [E-cadherin, vimentin, SNAIL/SLUG, AKT, phosphorylated (p)AKT, SMAD2/3 and pSMAD2/3] were performed after 72-h treatment. In silico analysis (molecular docking) of HT was performed to evaluate the potential of HT to bind with the TGFβ receptor. The viability of the HT-treated RECs was concentration-dependent, where the median effective concentration (EC50) was 19.04 μg/mL. Testing of the effects of 1 and 10 µg/mL HT revealed that HT suppressed expression of the protein markers vimentin and SNAIL/SLUG while preserving E-cadherin protein expression. Supplementation with HT protected against SMAD and AKT pathway activation in the TGFβ1-induced RECs. Furthermore, HT demonstrated the potential to bind with ALK5 (a TGFβ receptor component) in comparison to oleuropein. TGFβ1-induced EMT in RECs and HT exerted a positive effect in modulating the effects of EMT.
Fulltext Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds

Razali RA, Lokanathan Y, Yazid MD, Ansari AS, Saim AB, Hj Idrus RB

Int J Mol Sci, 2019 Jul 16;20(14).
PMID: 31315241 DOI: 10.3390/ijms20143492

Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.
Fulltext Osteogenic Induction of Wharton's Jelly-Derived Mesenchymal Stem Cell for Bone Regeneration: A Systematic Review

Ansari AS, Yazid MD, Sainik NQAV, Razali RA, Saim AB, Idrus RBH

Stem Cells Int, 2018;2018:2406462.
PMID: 30534156 DOI: 10.1155/2018/2406462

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are emerging as a promising source for bone regeneration in the treatment of bone defects. Previous studies have reported the ability of WJ-MSCs to be induced into the osteogenic lineage. The purpose of this review was to systematically assess the potential of WJ-MSC differentiation into the osteogenic lineage. A comprehensive search was conducted in Medline via Ebscohost and Scopus, where relevant studies published between 1961 and 2018 were selected. The main inclusion criteria were that articles must be primary studies published in English evaluating osteogenic induction of WJ-MSCs. The literature search identified 92 related articles, but only 18 articles met the inclusion criteria. These include two animal studies, three articles containing both in vitro and in vivo assessments, and 13 articles on in vitro studies, all of which are discussed in this review. There were two types of osteogenic induction used in these studies, either chemical or physical. The studies demonstrate that WJ-MSCs are able to differentiate into osteogenic lineage and promote osteogenesis. In light of these observations, it is suggested that WJ-MSCs can be a potential source of stem cells for osteogenic induction, as an alternative to bone marrow-derived mesenchymal stem cells.
Pilot study of the sensitivity and specificity of the DNA integrity assay for stool-based detection of colorectal cancer in Malaysian patients

Yehya AH, Yusoff NM, Khalid IA, Mahsin H, Razali RA, Azlina F, et al.

Asian Pac J Cancer Prev, 2012;13(5):1869-72.
PMID: 22901138

BACKGROUND: To assess the diagnostic potential of tumor-associated high molecular weight DNA in stool samples of 32 colorectal cancer (CRC) patients compared to 32 healthy Malaysian volunteers by means of polymerase chain reaction (PCR).
METHODS: Stool DNA was isolated and tumor-associated high molecular weight DNA (1.476 kb fragment including exons 6-9 of the p53 gene) was amplified using PCR and visualized on ethidium bromide-stained agarose gels.
RESULTS: Out of 32 CRC patients, 18 were positive for the presence of high molecular weight DNA as compared to none of the healthy individuals, resulting in an overall sensitivity of 56.3% with 100% specificity. Out of 32 patients, 23 had tumor on the left side and 9 on the right side, 16 and 2 being respectively positive. This showed that high molecular weight DNA was significantly (p=0.022) more detectable in patients with left side tumor (69.6% vs 22.2%). Out of 32 patients, 22 had tumors larger than 1.0 cm, 18 of these (81.8%) being positive for long DNA as compared to not a single patient with tumor size smaller than 1.0 cm (p<0.001).
CONCLUSION: We detected CRC-related high molecular weight p53 DNA in stool samples of CRC patients with an overall sensitivity of 56.3% with 100% specificity, with a strong tumor size dependence.
Fulltext Homozygous Southeast Asian Ovalocytosis in five live-born neonates

Lavinya AA, Razali RA, Razak MA, Mohamed R, Moses EJ, Soundararajan M, et al.

Haematologica, 2021 06 01;106(6):1758-1761.
PMID: 33179475 DOI: 10.3324/haematol.2020.268581

Not available.
Fulltext Effect of Different Collection Times of Dermal Fibroblast Conditioned Medium (DFCM) on In Vitro Re-Epithelialisation Process

Abdul Ghani N', Razali RA, Chowdhury SR, Fauzi MB, Bin Saim A, Ruszymah BHI, et al.

Biomedicines, 2022 Dec 09;10(12).
PMID: 36551960 DOI: 10.3390/biomedicines10123203

A key event in wound healing is re-epithelialisation, which is mainly regulated via paracrine signalling of cytokines, chemokines, and growth factors secreted by fibroblasts. Fibroblast-secreted factors can be collected from the used culture medium, known as dermal fibroblast conditioned medium (DFCM). The goal of this study was to optimise the culture condition to acquire DFCM and evaluate its effect on keratinocyte attachment, proliferation, migration, and differentiation. Confluent fibroblasts were cultured with serum-free keratinocyte-specific (DFCM-KM) and fibroblast-specific (DFCM-FM) medium at different incubation times (Days 1, 2, and 3). DFCM collected after 3 days of incubation (DFCM-KM-3 and DFCM-FM-3) contained a higher protein concentration compared to other days. Supplementation of DFCM-KM-3 enhanced keratinocyte attachment, while DFCM-FM-3 significantly increased the keratinocyte wound-healing rate, with an increment of keratinocyte area and collective cell migration, which was distinctly different from DFCM-KM-3 or control medium. Further analysis confirmed that the presence of calcium at higher concentrations in DFCM-FM facilitated the changes. The confluent dermal fibroblasts after 3 days of incubation with serum-free culture medium produced higher proteins in DFCM, resulting in enhanced in vitro re-epithelialisation. These results suggest that the delivery of DFCM could be a potential treatment strategy for wound healing.
Fulltext Isolation of Vaginal Epithelial Cells: In Preparation of Autologous Vaginal Tissue Lining for Congenital Absence of Vagina Patients

Lih Yuan T, Sulaiman N, Nur Azurah AG, Maarof M, Razali RA, Koh B, et al.

Int J Mol Sci, 2023 May 15;24(10).
PMID: 37240142 DOI: 10.3390/ijms24108798

Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The case is seldom reported due to the low prevalence and sparse epidemiology studies worldwide. A potential solution for the disorder is neovaginal creation with in vitro cultured vaginal mucosa. Limited studies have reported its application, but none are reproducible or specific regarding the established processes for acquiring vaginal epithelial cells from vaginal biopsies. These research gaps were adequately answered with an epidemiology study of inpatient details in Hospital Canselor Tuanku Muhriz, Malaysia, established methods and outcomes of vaginal tissue processing and isolation, and characterization of vaginal epithelial cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and immunofluorescence assays. The reported evidence and speculation that the disorder arises because of a cellular transition event between epithelial and mesenchymal cells during the development of the Mullerian duct could be key in the creation of neovaginas using established culture procedures to improve surgical results and restore fertility.
Fulltext The potential of Olea europaea extracts to prevent TGFβ1-induced epithelial to mesenchymal transition in human nasal respiratory epithelial cells

Razali RA, Nik Ahmad Eid NAH, Jayaraman T, Amir Hassan MA, Azlan NQ, Ismail NF, et al.

BMC Complement Altern Med, 2018 Jun 26;18(1):197.
PMID: 29940929 DOI: 10.1186/s12906-018-2250-5

BACKGROUND: One of the molecular mechanisms involved in upper airway-related diseases is epithelial-to-mesenchymal transition (EMT). Olea europaea (OE) has anti-inflammatory properties and thus, great potential to prevent EMT. This study aimed to investigate the effect of OE on EMT in primary nasal human respiratory epithelial cells (RECs).
METHODS: Respiratory epithelial cells were isolated and divided into four groups: control (untreated), treated with 0.05% OE (OE group), EMT induced with 5 ng/ml of transforming growth factor beta-1 (TGFβ1 group) and treated with 5 ng/ml TGFβ1 + 0.05% OE (TGFβ1 + OE group). The effects of OE treatment on growth kinetics, morphology and protein expression in RECs were evaluated. Immunocytochemistry analysis was performed to quantitate the total percentage of E-cadherin and vimentin expression from day 1 to day 3.
RESULTS: There were no significant differences between untreated RECs and OE-treated RECs in terms of their morphology, growth kinetics and protein expression. Induction with TGFβ1 caused RECs to have an elongated spindle shape, a slower proliferation rate, a higher expression of vimentin and a lower expression of E-cadherin compared with the control. Cells in the TGFβ1 + OE group had similar epithelial shape to untreated group however it had no significant differences in their proliferation rate when compared to TGFβ1-induced RECs. Cells treated with TGFβ1 + OE showed significantly reduced expression of vimentin and increased expression of E-cadherin compared with the TGFβ1 group (P