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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 Attachment, Proliferation, and Morphological Properties of Human Dermal Fibroblasts on Ovine Tendon Collagen Scaffolds: A Comparative Study

Busra FM, Lokanathan Y, Nadzir MM, Saim A, Idrus RBH, Chowdhury SR

Malays J Med Sci, 2017 Mar;24(2):33-43.
PMID: 28894402 DOI: 10.21315/mjms2017.24.2.5

INTRODUCTION: Collagen type I is widely used as a biomaterial for tissue-engineered substitutes. This study aimed to fabricate different three-dimensional (3D) scaffolds using ovine tendon collagen type I (OTC-I), and compare the attachment, proliferation and morphological features of human dermal fibroblasts (HDF) on the scaffolds.
METHODS: This study was conducted between the years 2014 to 2016 at the Tissue Engineering Centre, UKM Medical Centre. OTC-I was extracted from ovine tendon, and fabricated into 3D scaffolds in the form of sponge, hydrogel and film. A polystyrene surface coated with OTC-I was used as the 2D culture condition. Genipin was used to crosslink the OTC-I. A non-coated polystyrene surface was used as a control. The mechanical strength of OTC-I scaffolds was evaluated. Attachment, proliferation and morphological features of HDF were assessed and compared between conditions.
RESULTS: The mechanical strength of OTC-I sponge was significantly higher than that of the other scaffolds. OTC-I scaffolds and the coated surface significantly enhanced HDF attachment and proliferation compared to the control, but no differences were observed between the scaffolds and coated surface. In contrast, the morphological features of HDF including spreading, filopodia, lamellipodia and actin cytoskeletal formation differed between conditions.
CONCLUSION: OTC-I can be moulded into various scaffolds that are biocompatible and thus could be suitable as scaffolds for developing tissue substitutes for clinical applications and in vitro tissue models. However, further study is required to determine the effect of morphological properties on the functional and molecular properties of HDF.
Fulltext Centella asiatica (L.)-Neurodifferentiated Mesenchymal Stem Cells Promote the Regeneration of Peripheral Nerve

Hussin HM, Lawi MM, Haflah NHM, Kassim AYM, Idrus RBH, Lokanathan Y

Tissue Eng Regen Med, 2020 04;17(2):237-251.
PMID: 32036567 DOI: 10.1007/s13770-019-00235-6

BACKGROUND: Centella asiatica (L.) is a plant with neuroprotective and neuroregenerative properties; however, its effects on the neurodifferentiation of mesenchymal stem cells (MSCs) and on peripheral nerve injury are poorly explored. This study aimed to investigate the effects of C. asiatica (L.)-neurodifferentiated MSCs on the regeneration of peripheral nerve in a critical-size defect animal model.
METHODS: Nerve conduit was developed using decellularised artery seeded with C. asiatica-neurodifferentiated MSCs (ndMSCs). A 1.5 cm sciatic nerve injury in Sprague-Dawley rat was bridged with reversed autograft (RA) (n = 3, the gold standard treatment), MSC-seeded conduit (MC) (n = 4) or ndMSC-seeded conduit (NC) (n = 4). Pinch test and nerve conduction study were performed every 2 weeks for a total of 12 weeks. At the 12th week, the conduits were examined by histology and transmission electron microscopy.
RESULTS: NC implantation improved the rats' sensory sensitivity in a similar manner to RA. At the 12th week, nerve conduction velocity was the highest in NC compared with that of RA and MC. Axonal regeneration was enhanced in NC and RA as shown by the expression of myelin basic protein (MBP). The average number of myelinated axons was significantly higher in NC than in MC but significantly lower than in RA. The myelin sheath thickness was higher in NC than in MC but lower than in RA.
CONCLUSION: NC showed promising effects on nerve regeneration and functional restoration similar to those of RA. These findings revealed the neuroregenerative properties of C. asiatica and its potential as an alternative strategy for the treatment of critical size nerve defect.
Collagen Type I: A Versatile Biomaterial

Chowdhury SR, Mh Busra MF, Lokanathan Y, Ng MH, Law JX, Cletus UC, et al.

Adv Exp Med Biol, 2018 10 26;1077:389-414.
PMID: 30357700 DOI: 10.1007/978-981-13-0947-2_21

Collagen type I is the most abundant matrix protein in the human body and is highly demanded in tissue engineering, regenerative medicine, and pharmaceutical applications. To meet the uprising demand in biomedical applications, collagen type I has been isolated from mammalians (bovine, porcine, goat and rat) and non-mammalians (fish, amphibian, and sea plant) source using various extraction techniques. Recent advancement enables fabrication of collagen scaffolds in multiple forms such as film, sponge, and hydrogel, with or without other biomaterials. The scaffolds are extensively used to develop tissue substitutes in regenerating or repairing diseased or damaged tissues. The 3D scaffolds are also used to develop in vitro model and as a vehicle for delivering drugs or active compounds.
Collagen-coated polylactic-glycolic acid (PLGA) seeded with neural-differentiated human mesenchymal stem cells as a potential nerve conduit

Sulong AF, Hassan NH, Hwei NM, Lokanathan Y, Naicker AS, Abdullah S, et al.

Adv Clin Exp Med, 2014 May-Jun;23(3):353-62.
PMID: 24979505

Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative.
Fulltext Concentration Dependent Effect of Human Dermal Fibroblast Conditioned Medium (DFCM) from Three Various Origins on Keratinocytes Wound Healing

Maarof M, Chowdhury SR, Saim A, Bt Hj Idrus R, Lokanathan Y

Int J Mol Sci, 2020 Apr 22;21(8).
PMID: 32331278 DOI: 10.3390/ijms21082929

Fibroblasts secrete many essential factors that can be collected from fibroblast culture medium, which is termed dermal fibroblast conditioned medium (DFCM). Fibroblasts isolated from human skin samples were cultured in vitro using the serum-free keratinocyte-specific medium (Epilife (KM1), or define keratinocytes serum-free medium, DKSFM (KM2) and serum-free fibroblast-specific medium (FM) to collect DFCM-KM1, DFCM-KM2, and DFCM-FM, respectively). We characterised and evaluated the effects of 100-1600 µg/mL DFCM on keratinocytes based on attachment, proliferation, migration and gene expression. Supplementation with 200-400 µg/mL keratinocyte-specific DFCM-KM1 and DFCM-KM2 enhanced the attachment, proliferation and migration of sub-confluent keratinocytes, whereas 200-1600 µg/mL DFCM-FM significantly increased the healing rate in the wound healing assay, and 400-800 µg/mL DFCM-FM was suitable to enhance keratinocyte attachment and proliferation. A real-time (RT2) profiler polymerase chain reaction (PCR) array showed that 42 genes in the DFCM groups had similar fold regulation compared to the control group and most of the genes were directly involved in wound healing. In conclusion, in vitro keratinocyte re-epithelialisation is supported by the fibroblast-secreted proteins in 200-400 µg/mL DFCM-KM1 and DFCM-KM2, and 400-800 µg/mL DFCM-FM, which could be useful for treating skin injuries.
Cryptocaryon irritans recombinant proteins as potential antigens for sero-surveillance of cryptocaryonosis

Lokanathan Y, Mohd-Adnan A, Kua BC, Nathan S

J Fish Dis, 2016 Sep;39(9):1069-83.
PMID: 27086498 DOI: 10.1111/jfd.12474

Cryptocaryonosis is a major problem for mariculture, and the absence of suitable sero-surveillance tools for the detection of cryptocaryonosis makes it difficult to screen Cryptocaryon irritans-infected fish, particularly asymptomatic fish. In this study, we proposed a serum-based assay using selected C. irritans proteins to screen infected and asymptomatic fish. Eight highly expressed genes were chosen from an earlier study on C. irritans expressed sequence tags and ciliate glutamine codons were converted to universal glutamine codons. The chemically synthesized C. irritans genes were then expressed in an Escherichia coli expression host under optimized conditions. Five C. irritans proteins were successfully expressed in E. coli and purified by affinity chromatography. These proteins were used as antigens in an enzyme-linked immunosorbent assay (ELISA) to screen sera from experimentally immunized fish and naturally infected fish. Sera from both categories of fish reacted equally well with the expressed C. irritans recombinant proteins as well as with sonicated theronts. This study demonstrated the utility of producing ciliate recombinant proteins in a heterologous expression host. An ELISA was successfully developed to diagnose infected and asymptomatic fish using the recombinant proteins as antigens.
Decellularization and genipin crosslinking of amniotic membrane suitable for tissue engineering applications

Gobinathan S, Zainol SS, Azizi SF, Iman NM, Muniandy R, Hasmad HN, et al.

J Biomater Sci Polym Ed, 2018 12;29(17):2051-2067.
PMID: 29983100 DOI: 10.1080/09205063.2018.1485814

Amniotic membrane has the potential to be used as scaffold in various tissue engineering applications. However, increasing its biostability at the same time maintaining its biocompatibility is important to enhance its usage as a scaffold. This studied characteristics genipin-crosslinked amniotic membrane as a bioscaffold. Redundant human amniotic membranes (HAM) divided into native (nAM), decellularized (dAM) and genipin-crosslinked (clAM) groups. The dAM and clAM group were decellularized using thermolysin (TL) and sodium hydroxide (NaOH) solution. Next, clAM group was crosslinked with 0.5% and 1.0% (w/v) genipin. The HAM was then studied for in vitro degradation, percentage of swelling, optical clarity, ultrastructure and mechanical strength. Meanwhile, fibroblasts isolated from nasal turbinates were then seeded onto nAM, dAM and clAM for biocompatibility studies. clAM had the slowest degradation rate and were still morphologically intact after 30 days of incubation in 0.01% collagenase type 1 solution. The dAM had a significantly highest percentage of swelling than other groups (p
Development and physicochemical analysis of genipin-crosslinked gelatine sponge as a potential resorbable nasal pack

Selvarajah J, Mh Busra MF, Bin Saim A, Bt Hj Idrus R, Lokanathan Y

J Biomater Sci Polym Ed, 2020 09;31(13):1722-1740.
PMID: 32458725 DOI: 10.1080/09205063.2020.1774841

Nasal injury following nasal surgery is an adverse consequence, and prompt treatment should be initiated. Nasal packing, either non-absorbable or absorbable, are commonly used after nasal surgery to prevent bleeding and promote wound healing. In the current study, a novel gelatine sponge crosslinked with genipin was evaluated for suitability to be used as nasal packing and compared to one of the frequently used commercial nasal packing made up of polyurethane. Gelatine at 7% and 10% (w/v) concentration were crosslinked with varying concentrations of genipin, 0.5%, 0.25%, and 0.2% (v/v). The gelatine sponges were further characterised by its water uptake ability, biodegradation, water vapour transmission rate, porosity, contact angle, chemical composition, crosslinking degree, and mechanical properties. The gelatine sponges absorbed five times more water than their dry weight and were degraded within five days. The water vapour transmission rate of the gelatine sponges was 1187.7 ± 430.2 g/(m-2 day) for 7% gelatine and 779.4 ± 375.5 g/(m-2 day) for 10% gelatine. Crosslinking of gelatine with genipin resulted in lower porosity and did not affect the wettability of gelatine sponge (contact angle: 95.3 ± 12.1° for 7% gelatine and 88.4 ± 7.2° for 10% gelatine). In terms of biodegradability, the gelatine sponges took 24-48 h to degrade completely. Genipin crosslinking improved the degradation resistance and mechanical strength of gelatine sponge. The physical and chemical properties of the gelatine sponge, i.e. biodegradability and mechanical durability, support its potential as nasal packing.
Fulltext Effect of Growth Factor Supplementation on the Hair Cell Specific Markers of Cells Harvested from Basilar Membrane

Ubaidah MA, Chua KH, Ami M, Zainal A, Saim A, Saim L, et al.

J Int Adv Otol, 2015 Apr;11(1):23-9.
PMID: 26223713 DOI: 10.5152/iao.2015.539

Loss of auditory hair cells is a major cause of deafness. The presence of auditory progenitor cells in the inner ear raises the hope for mammalian inner ear cell regeneration. In this study, we aimed to investigate the effect of growth factor supplementations, namely a combination of epidermal growth factor (EGF), insulin-like growth factor (IGF), and beta (β)-fibroblast growth factor (βFGF), on the expression of hair cell-specific markers by cells harvested from the cochlear membrane. This would provide an insight into the capability of these cells to differentiate into hair cells.
Fulltext Electrospun Fiber-Coated Human Amniotic Membrane: A Potential Angioinductive Scaffold for Ischemic Tissue Repair

Hasmad HN, Bt Hj Idrus R, Sulaiman N, Lokanathan Y

Int J Mol Sci, 2022 Feb 03;23(3).
PMID: 35163664 DOI: 10.3390/ijms23031743

Cardiac patch implantation helps maximize the paracrine function of grafted cells and serves as a reservoir of soluble proangiogenic factors required for the neovascularization of infarcted hearts. We have previously fabricated a cardiac patch, EF-HAM, composed of a human amniotic membrane (HAM) coated with aligned PLGA electrospun fibers (EF). In this study, we aimed to evaluate the biocompatibility and angiogenic effects of EF-HAM scaffolds with varying fiber thicknesses on the paracrine behavior of skeletal muscle cells (SkM). Conditioned media (CM) obtained from SkM-seeded HAM and EF-HAM scaffolds were subjected to multiplex analysis of angiogenic factors and tested on HUVECs for endothelial cell viability, migration, and tube formation analyses. All three different groups of EF-HAM scaffolds demonstrated excellent biocompatibility with SkM. CM derived from SkM-seeded EF-HAM 7 min scaffolds contained significantly elevated levels of proangiogenic factors, including angiopoietin-1, IL-8, and VEGF-C compared to plain CM, which was obtained from SkM cultured on the plain surface. CM obtained from all SkM-seeded EF-HAM scaffolds significantly increased the viability of HUVECs compared to plain CM after five days of culture. However, only EF-HAM 7 min CM induced a higher migration capacity in HUVECs and formed a longer and more elaborate capillary-like network on Matrigel compared with plain CM. Surface roughness and wettability of EF-HAM 7 min scaffolds might have influenced the proportion of skeletal myoblasts and fibroblasts growing on the scaffolds and subsequently potentiated the angiogenic paracrine function of SkM. This study demonstrated the angioinductive properties of EF-HAM composite scaffold and its potential applications in the repair and regeneration of ischemic tissues.
Fulltext Hybrid Collagen Hydrogel/Chondroitin-4-Sulphate Fortified with Dermal Fibroblast Conditioned Medium for Skin Therapeutic Application

Maarof M, Mohd Nadzir M, Sin Mun L, Fauzi MB, Chowdhury SR, Idrus RBH, et al.

Polymers (Basel), 2021 Feb 08;13(4).
PMID: 33567703 DOI: 10.3390/polym13040508

The current strategy for rapid wound healing treatment involves combining a biomaterial and cell-secreted proteins or biomolecules. This study was aimed at characterizing 3-dimensional (3D) collagen hydrogels fortified with dermal fibroblast-conditioned medium (DFCM) as a readily available acellular skin substitute. Confluent fibroblasts were cultured with serum-free keratinocyte-specific medium (KM1 and KM2) and fibroblast-specific medium (FM) to obtain DFCM. Subsequently, the DFCM was mixed with collagen (Col) hydrogel and chondroitin-4-sulphate (C4S) to fabricate 3D constructs termed Col/C4S/DFCM-KM1, Col/C4S/DFCM-KM2, and Col/C4S/DFCM-FM. The constructs successfully formed soft, semi-solid and translucent hydrogels within 1 h of incubation at 37 °C with strength of <2.5 Newton (N). The Col/C4S/DFCM demonstrated significantly lower turbidity compared to the control groups. The Col/C4S/DFCM also showed a lower percentage of porosity (KM1: 35.15 ± 9.76%; KM2: 6.85 ± 1.60%; FM: 14.14 ± 7.65%) compared to the Col (105.14 ± 11.87%) and Col/C4S (143.44 ± 27.72%) constructs. There were no changes in both swelling and degradation among all constructs. Fourier transform infrared spectrometry showed that all groups consisted of oxygen-hydrogen bonds (O-H) and amide I, II, and III. In conclusion, the Col/C4S/DFCM constructs maintain the characteristics of native collagen and can synergistically deliver essential biomolecules for future use in skin therapeutic applications.
Fulltext In Vitro Evaluation of Biomaterials for Vocal Fold Injection: A Systematic Review

Wan-Chiew N, Baki MM, Fauzi MB, Lokanathan Y, Azman M

Polymers (Basel), 2021 Aug 06;13(16).
PMID: 34451158 DOI: 10.3390/polym13162619

Vocal fold injection is a preferred treatment in glottic insufficiency because it is relatively quick and cost-saving. However, researchers have yet to discover the ideal biomaterial with properties suitable for human vocal fold application. The current systematic review employing PRISMA guidelines summarizes and discusses the available evidence related to outcome measures used to characterize novel biomaterials in the development phase. The literature search of related articles published within January 2010 to March 2021 was conducted using Scopus, Web of Science (WoS), Google Scholar and PubMed databases. The search identified 6240 potentially relevant records, which were screened and appraised to include 15 relevant articles based on the inclusion and exclusion criteria. The current study highlights that the characterization methods were inconsistent throughout the different studies. While rheologic outcome measures (viscosity, elasticity and shear) were most widely utilized, there appear to be no target or reference values. Outcome measures such as cellular response and biodegradation should be prioritized as they could mitigate the clinical drawbacks of currently available biomaterials. The review suggests future studies to prioritize characterization of the viscoelasticity (to improve voice outcomes), inflammatory response (to reduce side effects) and biodegradation (to improve longevity) profiles of newly developed biomaterials.
Fulltext In vitro evaluation of genipin-crosslinked gelatin hydrogels for vocal fold injection

Ng WC, Lokanathan Y, Fauzi MB, Baki MM, Zainuddin AA, Phang SJ, et al.

Sci Rep, 2023 Mar 29;13(1):5128.
PMID: 36991038 DOI: 10.1038/s41598-023-32080-y

Glottic insufficiency is one of the voice disorders affecting all demographics. Due to the incomplete closure of the vocal fold, there is a risk of aspiration and ineffective phonation. Current treatments for glottic insufficiency include nerve repair, reinnervation, implantation and injection laryngoplasty. Injection laryngoplasty is favored among these techniques due to its cost-effectiveness and efficiency. However, research into developing an effective injectable for the treatment of glottic insufficiency is currently lacking. Therefore, this study aims to develop an injectable gelatin (G) hydrogel crosslinked with either 1-ethyl-3-(3-dimethylaminpropyl)carbodiimide hydrochloride) (EDC) or genipin (gn). The gelation time, biodegradability and swelling ratio of hydrogels with varying concentrations of gelatin (6-10% G) and genipin (0.1-0.5% gn) were investigated. Some selected formulations were proceeded with rheology, pore size, chemical analysis and in vitro cellular activity of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs), to determine the safety application of the selected hydrogels, for future cell delivery prospect. 6G 0.4gn and 8G 0.4gn were the only hydrogel groups capable of achieving complete gelation within 20 min, exhibiting an elastic modulus between 2 and 10 kPa and a pore size between 100 and 400 μm. Moreover, these hydrogels were biodegradable and biocompatible with WJMSCs, as > 70% viability were observed after 7 days of in vitro culture. Our results suggested 6G 0.4gn and 8G 0.4gn hydrogels as potential cell encapsulation injectates. In light of these findings, future research should focus on characterizing their encapsulation efficiency and exploring the possibility of using these hydrogels as a drug delivery system for vocal fold treatment.
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.
Large-Scale Expansion of Human Mesenchymal Stem Cells

Hassan MNFB, Yazid MD, Yunus MHM, Chowdhury SR, Lokanathan Y, Idrus RBH, et al.

Stem Cells Int, 2020;2020:9529465.
PMID: 32733574 DOI: 10.1155/2020/9529465

Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.
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.
Mesenchymal stem cell-derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy

Ling MTM, Govindaraju K, Lokanathan Y, Abidin AZ, Ibrahim B

Cell Biochem Funct, 2023 Dec;41(8):1044-1059.
PMID: 37933415 DOI: 10.1002/cbf.3881

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%-25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy, promising a holistic shift. MSC-EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC-EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC-EVs therapy for treating MetS.
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 Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review

Chan AML, Cheah JM, Lokanathan Y, Ng MH, Law JX

Int J Mol Sci, 2023 Feb 16;24(4).
PMID: 36835438 DOI: 10.3390/ijms24044026

Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers. However, these treatments cause a significant number of side effects, as they damage both the cancer cells and the actively dividing normal cells indiscriminately. Hence, a new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8+ T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects. However, the progression of cell-based immunotherapy is hindered by the combined action of TME and TD-EVs, which render the cancer cells less immunogenic. Recently, there has been an increase in interest in using immune cell derivatives to treat cancers. One of the highly potential immune cell derivatives is the NK cell-derived EVs (NK-EVs). As an acellular product, NK-EVs are resistant to the influence of TME and TD-EVs, and can be designed for "off-the-shelf" use. In this systematic review, we examine the safety and efficacy of NK-EVs to treat various cancers in vitro and in vivo.

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