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Fulltext The Anti-Viral and Anti-Inflammatory Properties of Edible Bird's Nest in Influenza and Coronavirus Infections: From Pre-Clinical to Potential Clinical Application

Chua KH, Mohamed IN, Mohd Yunus MH, Shafinaz Md Nor N, Kamil K, Ugusman A, et al.

Front Pharmacol, 2021;12:633292.
PMID: 34025406 DOI: 10.3389/fphar.2021.633292

Edible bird's nest (BN) is a Chinese traditional medicine with innumerable health benefits, including anti-viral, anti-inflammatory, neuroprotective, and immunomodulatory effects. A small number of studies have reported the anti-viral effects of EBN against influenza infections using in vitro and in vivo models, highlighting the importance of sialic acid and thymol derivatives in their therapeutic effects. At present, studies have reported that EBN suppresses the replicated virus from exiting the host cells, reduces the viral replication, endosomal trafficking of the virus, intracellular viral autophagy process, secretion of pro-inflammatory cytokines, reorient the actin cytoskeleton of the infected cells, and increase the lysosomal degradation of viral materials. In other models of disease, EBN attenuates oxidative stress-induced cellular apoptosis, enhances proliferation and activation of B-cells and their antibody secretion. Given the sum of its therapeutic actions, EBN appears to be a candidate that is worth further exploring for its protective effects against diseases transmitted through air droplets. At present, anti-viral drugs are employed as the first-line defense against respiratory viral infections, unless vaccines are available for the specific pathogens. In patients with severe symptoms due to exacerbated cytokine secretion, anti-inflammatory agents are applied. Treatment efficacy varies across the patients, and in times of a pandemic like COVID-19, many of the drugs are still at the experimental stage. In this review, we present a comprehensive overview of anti-viral and anti-inflammatory effects of EBN, chemical constituents from various EBN preparation techniques, and drugs currently used to treat influenza and novel coronavirus infections. We also aim to review the pathogenesis of influenza A and coronavirus, and the potential of EBN in their clinical application. We also describe the current literature in human consumption of EBN, known allergenic or contaminant presence, and the focus of future direction on how these can be addressed to further improve EBN for potential clinical application.
Fulltext Laboratory Evaluation of a Rapid IgG4 Antibody Test (BLF Rapid™) for Bancroftian Filariasis

Noordin R, Yunus MH, Robinson K, Won KY, Babu S, Fischer PU, et al.

Am J Trop Med Hyg, 2018 12;99(6):1587-1590.
PMID: 30350768 DOI: 10.4269/ajtmh.18-0566

At the end phase of the Global Programme to Eliminate Lymphatic Filariasis, antibody testing may have a role in decision-making for bancroftian filariasis-endemic areas. This study evaluated the diagnostic performance of BLF Rapid™, a prototype immunochromatographic IgG4-based test using BmSXP recombinant protein, for detection of bancroftian filariasis. The test was evaluated using 258 serum samples, comprising 96 samples tested at Universiti Sains Malaysia (in-house) and 162 samples tested independently at three international laboratories in the USA and India, and two laboratories in Malaysia. The independent testing involved 99 samples from Wuchereria bancrofti microfilaria or antigen positive individuals and 63 samples from people who were healthy or had other infections. The in-house evaluation showed 100% diagnostic sensitivity and specificity. The independent evaluations showed a diagnostic sensitivity of 84-100% and 100% specificity (excluding non-lymphatic filarial infections). BLF Rapid has potential as a surveillance diagnostic tool to make "Transmission Assessment Survey"-stopping decisions and conduct post-elimination surveillance.
Fulltext Identification and Preliminary Evaluation of a Novel Recombinant Protein for Serodiagnosis of Strongyloidiasis

Arifin N, Yunus MH, Nolan TJ, Lok JB, Noordin R

Am J Trop Med Hyg, 2018 04;98(4):1165-1170.
PMID: 29436335 DOI: 10.4269/ajtmh.17-0697

Strongyloides stercoralis is a human parasite that can cause a long-term infection. In immunosuppressed patients, strongyloidiasis may be fatal when there is overwhelming autoinfection resulting in the migration of large numbers of larvae through many organs. Definitive diagnosis is still a challenge, and a combination of symptoms, microscopic identification, and serology test results are often used to arrive at a clinical decision. However, intermittent larval excretion, low parasite burden, and occult infections are challenges with parasitological diagnosis of infection with S. stercoralis. Meanwhile, serologic tests using immunoglobulin G and parasite antigen extract have problems of cross-reactivity with other helminthic infections. Recombinant antigen-based serodiagnosis is a good alternative to overcome the laboratory diagnostic issues. Herein, we report on the isolation of cDNA clone encoding an antigen of potential diagnostic value identified from immunoscreening of a S. stercoralis cDNA library. The translated protein had highest similarity to Strongyloides ratti immunoglobulin-binding protein 1. The recombinant antigen produced, rSs1a, was assessed using western blot and enzyme-linked immunosorbent assay. The latter showed 96% diagnostic sensitivity and 93% specificity; thus, rSs1a has good potential for use in serodiagnosis of human strongyloidiasis.
Production of Toxocara cati TES-120 Recombinant Antigen and Comparison with its T. canis Homolog for Serodiagnosis of Toxocariasis

Zahabiun F, Sadjjadi SM, Yunus MH, Rahumatullah A, Moghaddam MH, Saidin S, et al.

Am J Trop Med Hyg, 2015 Aug;93(2):319-25.
PMID: 26033026 DOI: 10.4269/ajtmh.15-0190

Toxocariasis is a cosmopolitan zoonotic disease caused by the infective larvae of Toxocara canis and T. cati. Diagnosis in humans is usually based on clinical symptoms and serology. Immunoglobulin G (IgG)-enzyme-linked immunosorbent assay kits using T. canis excretory-secretory (TES) larval antigens are commonly used for serodiagnosis. Differences in the antigens of the two Toxocara species may influence the diagnostic sensitivity of the test. In this study, T. cati recombinant TES-120 (rTES-120) was cloned, expressed, and compared with its T. canis homolog in an IgG4-western blot. The diagnostic sensitivity and specificity of T. cati rTES-120 were 70% (33/47) and 100% (39/39), respectively. T. canis rTES-120 showed 57.4% sensitivity and 94.4% specificity. When the results of assays using rTES-120 of both species were considered, the diagnostic sensitivity was 76%. This study shows that using antigens from both Toxocara species may improve the serodiagnosis of toxocariasis.
Fulltext Lateral flow test using Echinococcus granulosus native antigen B and comparison of IgG and IgG4 dipsticks for detection of human cystic echinococcosis

Khalilpour A, Sadjjadi SM, Moghadam ZK, Yunus MH, Zakaria ND, Osman S, et al.

Am J Trop Med Hyg, 2014 Nov;91(5):994-9.
PMID: 25200268 DOI: 10.4269/ajtmh.14-0170

Cystic echinococcosis (CE) caused by infection with Echinococcus granulosus is of major concern for humans in many parts of the world. Antigen B was prepared from E. granulosus hydatid fluid, and Western blots confirmed eight batches showing a band corresponding to the 8-/12-kDa subunit with positive serum and no low-molecular mass band (< 15 kDa) with negative serum. The batches were pooled and used to prepare lateral flow immunoglobulin G4 (IgG4) and IgG dipsticks. Diagnostic sensitivity was determined using serum samples from 21 hydatidosis patients, and diagnostic specificity was established using sera from 17 individuals infected with other parasites and 15 healthy people. IgG4 dipstick had a diagnostic sensitivity of 95% (20 of 21) and a specificity of 100% (32 of 32). The IgG dipstick had a sensitivity of 100% (21 of 21) and a specificity of 87.5% (28 of 32). Thus, both IgG and IgG4 dipsticks had high sensitivities, but IgG4 had greater specificity for the diagnosis of human CE.
Fulltext Identification and real-time expression analysis of selected Toxoplasma gondii in-vivo induced antigens recognized by IgG and IgM in sera of acute toxoplasmosis patients

Amerizadeh A, Khoo BY, Teh AY, Golkar M, Abdul Karim IZ, Osman S, et al.

BMC Infect Dis, 2013;13:287.
PMID: 23800344 DOI: 10.1186/1471-2334-13-287

Toxoplasma gondii is an obligate intracellular zoonotic parasite of the phylum Apicomplexa which infects a wide range of warm-blooded animals, including humans. In this study in-vivo induced antigens of this parasite was investigated using in-vivo induced antigen technology (IVIAT) and pooled sera from patients with serological evidence of acute infection.
Identification of Toxoplasma gondii in-vivo induced antigens by cDNA library immunoscreening with chronic toxoplasmosis sera

Amerizadeh A, Idris ZM, Khoo BY, Kotresha D, Yunus MH, Karim IZ, et al.

Microb Pathog, 2013 Jan;54:60-6.
PMID: 23044055 DOI: 10.1016/j.micpath.2012.09.006

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Chronically-infected individuals with a compromised immune system are at risk for reactivation of the disease. In-vivo induced antigen technology (IVIAT) is a promising method for the identification of antigens expressed in-vivo. The aim of the present study was to apply IVIAT to identify antigens which are expressed in-vivo during T. gondii infection using sera from individuals with chronic toxoplasmosis. Forty serum samples were pooled, pre-adsorped against three different preparations of antigens, from each in-vitro grown T. gondii and Escherichia coli XLBlue MRF', and then used to screen a T. gondii cDNA expression library. Sequencing of DNA inserts from positive clones showed eight open reading frames with high homology to T. gondii genes. Expression analysis using quantitative real-time PCR showed that SAG1-related sequence 3 (SRS3) and two hypothetical genes were up-regulated in-vivo relative to their expression levels in-vitro. These three proteins also showed high sensitivity and specificity when tested with individual serum samples. Five other proteins namely M16 domain peptidase, microneme protein, elongation factor 1-alpha, pre-mRNA-splicing factor and small nuclear ribonucleoprotein F had lower RNA expression in-vivo as compared to in-vitro. SRS3 and the two hypothetical proteins warrant further investigation into their roles in the pathogenesis of toxoplasmosis.
IgG avidity Western blot using Toxoplasma gondii rGRA-7 cloned from nucleotides 39-711 for serodiagnosis of acute toxoplasmosis

Deshpande PS, Kotresha D, Noordin R, Yunus MH, Saadatnia G, Golkar M, et al.

Rev Inst Med Trop Sao Paulo, 2013 4 9;55(2):79-83.
PMID: 23563759

Toxoplasmosis is an important cause of congenital infection. The present study was performed to evaluate the usefulness of recombinant (r) GRA-7 cloned from nucleotides (n) 39-711 in discriminating between acute and chronic toxoplasmosis. First, commercial IgM, IgG and IgG avidity ELISAs were used to determine the serological profile of the sera. Serum samples were from 20 symptomatic patients with acute infection (low IgG avidity, IgM positive), 10 with chronic infection (high IgG avidity, IgM negative) and 10 with indeterminate IgG avidity (IgM positive) which were tested for IgG avidity status with an in-house developed IgG avidity Western blot using the rGRA-7 recombinant antigen. All 20 sera from cases of probable acute infection showed bands which either faded out completely or reduced significantly in intensity after treatment with 8 M urea, whereas the band intensities of the 10 serum samples from chronic cases remained the same. Of the 10 sera with indeterminate IgG avidity status, after treatment with 8 M urea the band intensities with six sera remained the same, two sera had completely faded bands and another two sera had significantly reduced band intensities. Discrimination between acute and chronic toxoplasmosis was successfully performed by the in-house IgG avidity Western blot.
Fulltext The Association between Inflammation and Pulse Wave Velocity in Dyslipidemia: An Evidence-Based Review

Aminuddin A, Lazim MRMLM, Hamid AA, Hui CK, Mohd Yunus MH, Kumar J, et al.

Mediators Inflamm, 2020;2020:4732987.
PMID: 32908450 DOI: 10.1155/2020/4732987

Dyslipidemia is associated with increased arterial stiffness (AS) which may lead to hypertension. Among the methods to assess AS are carotid-femoral and brachial-ankle pulse wave velocity. Dyslipidemia is also known to trigger inflammation. C-reactive protein (CRP) is one of the commonest inflammatory markers measured in the clinical setting. However, the association between inflammation and pulse wave velocity (PWV) in people with dyslipidemia is less studied. Therefore, this review investigated the association between inflammation (as measured by CRP) and PWV in dyslipidemia patients. The search of the literature was conducted via PubMed and Scopus database. The keywords used were "aortic stiffness" OR "arterial stiffness" OR "pulse wave velocity" OR "vascular stiffness" OR "carotid femoral pulse wave velocity" OR "pulse wave analysis" AND "inflammation" OR "c reactive protein" OR "c-reactive protein" OR "high sensitivity c reactive protein" AND "dyslipidemia" OR "hyperlipidemia" OR "hypercholesterolemia" OR "hyperlipoproteinemia" OR "hypertriglyceridemia". The following criteria were used: (1) only full-length original articles published in English language, (2) articles that reported the association between arterial stiffness measured as carotid-femoral PWV (cfPWV) or brachial-ankle PWV (baPWV) and CRP or high-sensitivity CRP, and (3) study involving human subjects. The search identified 957 articles published between 1980 and February 2020. Only eight articles fulfilled the inclusion criteria and were used for data extraction. Five of the studies were cross-sectional studies while another three studies were interventional studies. Seven out of eight papers found a significant positive association between AS and CRP, and the correlation ranged from mild to moderate association (Pearson r = 0.33 to r = 0.624). In conclusion, inflammation is associated with increased PWV in patients with dyslipidemia. This supports the involvement of inflammation in the development of AS in dyslipidemia.
Massive Traumatic Skin Defect Successfully Treated with Autologous, Bilayered, Tissue-Engineered MyDerm Skin Substitute: A Case Report

Mohamed Haflah NH, Ng MH, Mohd Yunus MH, Naicker AS, Htwe O, Abdul Razak KA, et al.

JBJS Case Connect, 2018 6 15;8(2):e38.
PMID: 29901479 DOI: 10.2106/JBJS.CC.17.00250

CASE: A 22-year-old man sustained a laceration that measured 180 cm, after debridement, over the anterolateral aspect of the right leg following a road traffic accident. The wound was treated with MyDerm (Universiti Kebangsaan Malaysia), a cell-based, bilayered, bioengineered dermal substitute that contains no animal-derived components and is fully autologous. For its construction, only a small area of skin was harvested from the left groin, which was closed primarily with absorbable sutures.
CONCLUSION: MyDerm is an alternative option for the treatment of a massive skin defect in patients who desire removal of only a negligible amount of skin from the donor site and when use of an autograft is insufficient.
Isolation and characterization of ssDNA aptamers against BipD antigen of Burkholderia pseudomallei

Selvam K, Najib MA, Khalid MF, Yunus MH, Wahab HA, Harun A, et al.

Anal Biochem, 2024 Aug 28;695:115655.
PMID: 39214325 DOI: 10.1016/j.ab.2024.115655

BACKGROUND: Melioidosis is difficult to diagnose due to its wide range of clinical symptoms. The culture method is time-consuming and less sensitive, emphasizing the importance of rapid and accurate diagnostic tests for melioidosis. Burkholderia invasion protein D (BipD) of Burkholderia pseudomallei is a potential diagnostic biomarker. This study aimed to isolate and characterize single-stranded DNA aptamers that specifically target BipD.
METHODS: The recombinant BipD protein was produced, followed by isolation of BipD-specific aptamers using Systematic Evolution of Ligands by EXponential enrichment. The binding affinity and specificity of the selected aptamers were evaluated using Enzyme-Linked Oligonucleotide Assay.
RESULTS: The fifth SELEX cycle showed a notable enrichment of recombinant BipD protein-specific aptamers. Sequencing analysis identified two clusters with a total of seventeen distinct aptamers. AptBipD1, AptBipD13, and AptBipD50 were chosen based on their frequency. Among them, AptBipD1 exhibited the highest binding affinity with a Kd value of 1.0 μM for the recombinant BipD protein. Furthermore, AptBipD1 showed significant specificity for B. pseudomallei compared to other tested bacteria.
CONCLUSION: AptBipD1 is a promising candidate for further development of reliable, affordable, and efficient point-of-care diagnostic tests for melioidosis.
Fulltext Multi-Laboratory Evaluation of a Lateral Flow Rapid Test for Detection of Amebic Liver Abscess

Noordin R, Yunus MH, Saidin S, Mohamed Z, Fuentes Corripio I, Rubio JM, et al.

Am J Trop Med Hyg, 2020 12;103(6):2233-2238.
PMID: 32996457 DOI: 10.4269/ajtmh.20-0348

Independent evaluations of XEh Rapid®, an IgG4-based rapid dipstick test, were performed to assess its diagnostic performance to detect amebic liver abscess (ALA) using 405 samples at seven laboratories in four countries. The test showed high diagnostic specificity (97-100%) when tested with samples from healthy individuals (n = 100) and patients with other diseases (n = 151). The diagnostic sensitivity was tested with a total of 154 samples, and the results were variable. It was high in three laboratories (89-94%), and moderate (72%) and low (38%) in two other laboratories. Challenges and issues faced in the evaluation process are discussed. Nevertheless, XEh Rapid is promising to be developed into a point-of-care test in particular for resource-limited settings, and thus merits further confirmation of its diagnostic sensitivity.
Fulltext Diagnostic Potential of an IgE-ELISA in Detecting Strongyloidiasis

Ahmad H, Balachandra D, Arifin N, Nolan TJ, Lok JB, Hayat Khan A, et al.

Am J Trop Med Hyg, 2020 12;103(6):2288-2293.
PMID: 32996454 DOI: 10.4269/ajtmh.20-0265

Strongyloides stercoralis infection is prevalent worldwide and can cause lifelong infection in immunocompetent individuals, and potentially death in immunosuppressed patients. The diagnosis is hindered by the low sensitivity of microscopic examination, thus making serology an important complementary test to improve the detection rate. However, there were reports that some Strongyloides-infected individuals were negative with specific IgG and IgG4 assays, and other helminth infections were positive with commercial Strongyloides IgG-ELISAs. Thus, there is a need to develop better serodiagnostic methods for strongyloidiasis. We investigated the diagnostic potential of IgE-ELISAs using Strongyloides larval lysate. Sera from two groups infected with Strongyloides served as the positive reference, that is, 1) positive by commercial IgG-ELISAs and IgG4 rapid test, and stool samples positive by microscopy and/or PCR (group IA; n = 20); and 2) negative by IgG-ELISAs and IgG4 rapid test, but stool samples were PCR positive (group IB sera; n = 11). Sera from another two groups served as negative reference (controls), that is, 1) infected with other parasites (group II; n = 73) and 2) healthy donors (group III; n = 22). Results showed a 100% diagnostic sensitivity in detecting sera from groups IA and IB. The latter group of individuals probably had early infection because their IgG and IgG4 assays were negative. The optical density values of group IB sera were also significantly lower than those of group IA (P < 0.003). The IgE-ELISA was 100% specific when tested against sera from groups II and III. This study highlights the diagnostic potential of IgE-ELISA using larval lysate to detect strongyloidiasis, especially those with probable early infection.
The effects of human serum to the morphology, proliferation and gene expression level of the respiratory epithelium in vitro

Yunus MH, Siang KC, Hashim NI, Zhi NP, Zamani NF, Sabri PP, et al.

Tissue Cell, 2014 Aug;46(4):233-40.
PMID: 24973262 DOI: 10.1016/j.tice.2014.05.003

The culture of human airway epithelial cells has played an important role in advancing our understanding of the metabolic and molecular mechanisms underlying normal function and disease pathology of airway epithelial cells. The present study focused on investigating the effects of human serum (HS) on the qualitative and quantitative properties of the human respiratory epithelium compared to the fetal bovine serum (FBS), as a supplement in culture. Respiratory epithelial (RE) cells derived from human nasal turbinate were co-cultured with fibroblasts, subsequently separated at 80-90% confluency by differential trypsinization. RE cells were then sub-cultured into 2 different plates containing 5% allogenic HS and FBS supplemented media respectively up to passage 1 (P1). Cell morphology, growth rate, cell viability and population doubling time were assessed under light microscope, and levels of gene expression were measured via real time reverse transcriptase-polymerase chain reaction (qRT-PCR). RE cells appeared as polygonal shape and expanded when cultured in HS whereas RE cells in FBS were observed to be easily matured thus limit the RE cells expansion. Proliferation rate of RE cells in HS supplemented media (7673.18 ± 1207.15) was 3 times higher compared to RE in FBS supplemented media (2357.68 ± 186.85). Furthermore, RE cells cultured in HS-supplemented media required fewer days (9.15 ± 1.10) to double in numbers compared to cells cultured in FBS-supplemented media (13.66 ± 0.81). Both the differences were significant (p<0.05). However, there were no significant differences in the viability of RE cells in both groups (p=0.105). qRT-PCR showed comparable expressions of gene Cytokeratin-14 (CK-14), Cytokeratin-18 (CK-18) and Mucin-5 subtype B (MUC5B) in RE cells cultured in both groups (p>0.05). In conclusion, HS is a comparatively better choice of media supplement in accelerating growth kinetics of RE cells in vitro thus producing a better quality of respiratory epithelium for future tracheal reconstruction.
Fulltext Physicochemical Characterization of Bilayer Hybrid Nanocellulose-Collagen as a Potential Wound Dressing

Ooi KS, Haszman S, Wong YN, Soidin E, Hesham N, Mior MAA, et al.

Materials (Basel), 2020 Sep 30;13(19).
PMID: 33007893 DOI: 10.3390/ma13194352

The eminent aim for advance wound management is to provide a great impact on the quality of life. Therefore, an excellent strategy for an ideal wound dressing is being developed that eliminates certain drawbacks while promoting tissue regeneration for the prevention of bacterial invasion. The aim of this study is to develop a bilayer hybrid biomatrix of natural origin for wound dressing. The bilayer hybrid bioscaffold was fabricated by the combination of ovine tendon collagen type I and palm tree-based nanocellulose. The fabricated biomatrix was then post-cross-linked with 0.1% (w/v) genipin (GNP). The physical characteristics were evaluated based on the microstructure, pore size, porosity, and water uptake capacity followed by degradation behaviour and mechanical strength. Chemical analysis was performed using energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectrophotometry (FTIR), and X-ray diffraction (XRD). The results demonstrated a uniform interconnected porous structure with optimal pore size ranging between 90 and 140 μm, acceptable porosity (>70%), and highwater uptake capacity (>1500%). The biodegradation rate of the fabricated biomatrix was extended to 22 days. Further analysis with EDX identified the main elements of the bioscaffold, which contains carbon (C) 50.28%, nitrogen (N) 18.78%, and oxygen (O) 30.94% based on the atomic percentage. FTIR reported the functional groups of collagen type I (amide A: 3302 cm-1, amide B: 2926 cm-1, amide I: 1631 cm-1, amide II: 1547 cm-1, and amide III: 1237 cm-1) and nanocellulose (pyranose ring), thus confirming the presence of collagen and nanocellulose in the bilayer hybrid scaffold. The XRD demonstrated a smooth wavy wavelength that is consistent with the amorphous material and less crystallinity. The combination of nanocellulose with collagen demonstrated a positive effect with an increase of Young's modulus. In conclusion, the fabricated bilayer hybrid bioscaffold demonstrated optimum physicochemical and mechanical properties that are suitable for skin wound dressing.
Fulltext Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review

Chan AML, Ng AMH, Mohd Yunus MH, Idrus RBH, Law JX, Yazid MD, et al.

Nutrients, 2021 Jul 22;13(8).
PMID: 34444658 DOI: 10.3390/nu13082497

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling.
Fulltext Identification of potential dual -targets anti- toxoplasma gondii compounds through structure-based virtual screening and in-vitro studies

Salin NH, Noordin R, Al-Najjar BO, Kamarulzaman EE, Yunus MH, Karim IZA, et al.

PLoS One, 2020;15(5):e0225232.
PMID: 32442170 DOI: 10.1371/journal.pone.0225232

Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease which can lead to morbidity and mortality of the fetus and immunocompromised individuals. Due to the limited effectiveness or side effects of existing drugs, the search for better drug candidates is still ongoing. In this study, we performed structure-based screening of potential dual-targets inhibitors of active sites of T. gondii drug targets such as uracil phosphoribosyltransferase (UPRTase) and adenosine kinase (AK). First screening of virtual compounds from the National Cancer Institute (NCI) was performed via molecular docking. Subsequently, the hit compounds were tested in-vitro for anti- T. gondii effect using cell viability assay with Vero cells as host to determine cytotoxicity effects and drug selectivities. Clindamycin, as positive control, showed a selectivity index (SI) of 10.9, thus compounds with SI > 10.9 specifically target T. gondii proliferation with no significant effect on the host cells. Good anti- T. gondii effects were observed with NSC77468 (7-ethoxy-4-methyl-6,7-dihydro-5H-thiopyrano[2,3-d]pyrimidin-2-amine) which showed SI values of 25. This study showed that in-silico selection can serve as an effective way to discover potentially potent and selective compounds against T. gondii.
Stem cells as a potential therapy in managing various disorders of metabolic syndrome: a systematic review

Shamsuddin SA, Chan AML, Ng MH, Yazid MD, Law JX, Hj Idrus RB, et al.

Am J Transl Res, 2021;13(11):12217-12227.
PMID: 34956448

Recent explorations on mesenchymal stem/stromal cells (MSC) have reported a promising future for cell-based therapies. MSCs are widely sourced from various tissues and express unique properties of regenerative potential and immunomodulation. Currently, there is a growing interest in utilizing MSC for treatment of chronic diseases to overcome the drawbacks of chemical drugs. Metabolic Syndrome (MetS) is described as a cluster of metabolic abnormalities categorized as abdominal obesity, dyslipidaemia, hypertension, hypertriglyceridemia, and hyperglycaemia. Patients diagnosed with MetS have a high predisposition for developing cardiovascular complications, diabetes, non-alcoholic fatty liver diseases, bone loss, cancer, and mortality. Hence, research on MSC as therapy for MetS and related diseases, is greatly valued and are advantaged by the low immunogenicity with high regenerative capacity. However, there are many obstacles to be addressed such as the safety, efficacy, and consistency of different MSC sources. Additionally, factors such as effective dose level and delivery method are equally important to achieve uniform therapeutic outcomes. This systematic review discusses the potential roles of MSC in managing the multiple clusters of MetS. Research articles during the past 20 years were systematically searched and filtered to update the progress in the field of MSC therapy in managing various components of MetS. The different sources of MSC, dosage, method of delivery and outcome measures for the stem cell therapies were compiled from the systematically selected research articles. It can be concluded from the review of the selected articles that MSCs can improve the various disorders of MetS such as abdominal obesity, hyperglycaemia, hypertriglyceridemia and hypertension, and represent a promising alternative to conventional therapy of the MetS cluster.
The Use of Engineered Bilayered Skin (MyDermTM) in the Management of Massive Skin Defect in Grade III Gustilo-Anderson Open Fracture

Mohamed Haflah NH, Ng MH, Mohd Yunus MH, Naicker AS, Htwe O, Fahmi M, et al.

Int J Low Extrem Wounds, 2017 Sep;16(3):212-216.
PMID: 28862056 DOI: 10.1177/1534734617724974

Open fracture Gustilo-Anderson grade IIIC is associated with higher risk of infection and problems with soft tissue coverage. Various methods have been used for soft tissue coverage in open fractures with large skin defect. We report a case of a patient who had grade IIIC open fracture of the tibia with posterior tibial artery injury. The patient underwent external fixation and reduction. Because of potential compartment syndrome after vascular repair, fasciotomy of the posterior compartment was performed. This wound, however, became infected and because of further debridement, gave rise to a large skin defect. A tissue engineered skin construct, MyDermTM was employed to cover this large defect. Complete wound closure was achieved 35 days postimplantation. The patient then underwent plating of the tibia for nonunion with no adverse effect to the grafted site. The tibia eventually healed 5 months postplating, and the cosmetic appearance of the newly formed skin was satisfactory.
Fulltext A Three-Dimensional Xeno-Free Culture Condition for Wharton's Jelly-Mesenchymal Stem Cells: The Pros and Cons

Koh B, Sulaiman N, Fauzi MB, Law JX, Ng MH, Yuan TL, et al.

Int J Mol Sci, 2023 Feb 13;24(4).
PMID: 36835154 DOI: 10.3390/ijms24043745

Xeno-free three-dimensional cultures are gaining attention for mesenchymal stem cell (MSCs) expansion in clinical applications. We investigated the potential of xeno-free serum alternatives, human serum and human platelet lysate, to replace the current conventional use of foetal bovine serum for subsequent MSCs microcarrier cultures. In this study, Wharton's Jelly MSCs were cultured in nine different media combinations to identify the best xeno-free culture media for MSCs culture. Cell proliferation and viability were identified, and the cultured MSCs were characterised in accordance with the minimal criteria for defining multipotent mesenchymal stromal cells by the International Society for Cellular Therapy (ISCT). The selected culture media was then used in the microcarrier culture of MSCs to determine the potential of a three-dimensional culture system in the expansion of MSCs for future clinical applications, and to identify the immunomodulatory potential of cultured MSCs. Low Glucose DMEM (LG) + Human Platelet (HPL) lysate media appeared to be good candidates for replacing conventional MSCs culture media in our monolayer culture system. MSCs cultured in LG-HPL achieved high cell yield, with characteristics that remained as described by ISCT, although the overall mitochondrial activity of the cells was lower than the control and the subsequent effects remained unknown. MSC microcarrier culture, on the other hand, showed comparable cell characteristics with monolayer culture, yet had stagnated cell proliferation, which is potentially due to the inactivation of FAK. Nonetheless, both the MSCs monolayer culture and the microcarrier culture showed high suppressive activity on TNF-α, and only the MSC microcarrier culture has a better suppression of IL-1 secretion. In conclusion, LG-HPL was identified as a good xeno-free media for WJMSCs culture, and although further mechanistic research is needed, the results show that the xeno-free three-dimensional culture maintained MSC characteristics and improved immunomodulatory activities, suggesting the potential of translating the monolayer culture into this culture system in MSC expansion for future clinical application.

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