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Discrete event simulation and data envelopment analysis models for selecting the best resource allocation alternative at an emergency department’s green zone

Nazhatul Sahima Mohd Yusoff, Choong-Yeun Liong, Wan Rosmanira Ismail, Abu Yazid Md Noh

Sains Malaysiana, 2018;47:2917-2925.

The Green Zone of Emergency Department Hospital Universiti Sains Malaysia (EDHUSM) which provides treatment for
non-critical cases contributes partly to the hustle and bustle in the emergency department. The imbalance of doctors
and nurses with the patient ratio which forms the resources’ bottleneck further results to the long patients’ waiting time
especially after the office hours and during weekends and public holidays. Collectively, this disproportion and bottlenecks
roots up the current problem faced by Green Zone EDHUSM which constantly fails to achieve the KPIs set by the hospital.
Henceforth, this study focuses on the best resource allocation of doctors and nurses for shifts during the weekdays and
for shifts during weekends and public holidays. The hybrid method of Discrete Event Simulation, and Data Envelopment
Analysis models such as BCC-input oriented and Super-Efficiency, were deployed to obtain the best resource allocation
for the two groups of shift. The method produced a series of resources allocation alternatives for doctors and nurses
with a total of 64 alternatives for weekdays and 729 alternatives for weekends and public holidays. The results show that
the best allocation for doctors and nurses during weekdays are three doctors and three nurses serving for every shift,
while during weekends and public holidays, a combination of four doctors and four nurses for every shift are the best.
The proposed combinations have reduced the average waiting time, optimized the utilization of doctors and nurses, and
managed to increase the number of patients served during weekdays, weekends and public holidays.
Fulltext A descriptive study of decompression illness among scuba divers treated with hyperbaric oxygen therapy at a military hospital-based recompression facility in Peninsular Malaysia

Fazriyati Jamharee, Abu Yazid Md Noh, Tuan Hairulnizam Tuan Kamauzaman, Ariff Arithra Abdullah, Junainah Nor

Malaysian Journal of Emergency Medicine, 2016;1(1):11-23.
MyJurnal

Background: Diving related illness has become a public health concern, as there isan increasing number of diversworldwide. However, the incidence of Decompression Illness (DCI), a medical disorder as a result of sudden reduction of ambient pressure, remainsgenerallylow. This paper describes the patternsof decompression illness treated in a military hospital-based recompression chamber facility in Peninsular Malaysiafrom year 2000 until 2010.Objective:The objective ofthis study is to determine the patternsof decompression illnesspatientstreated withHyperbaric Oxygen Therapy(HBOT)in a military hospital-based recompression chamber facility inPeninsular Malaysia.
Methodology:A retrospective descriptive study was carried out to utilizesecondary data from Hospital Angkatan Tentera Lumut, Perakfrom 1stJanuary 2000 to 31stDecember 2010. A total of 96 caseswere included in thisstudy.
Results:Most of the patients were male (94.8%), recreational divers (43.0%), non-smokers (56.3%),with no previous medical illness(85.4%), who had dived with compressed air (78.0%), had lessthan 5years divingexperience (56.3%), were non-instructors(75.0%),and had body mass index between 18.5 to 24.9kg/m2(59.4%). Interestingly,25% of the patients developing DCI dived to less than 10 meters depth, 35.4% of them went for a single dive and 71.9% performed safety stops.The majority of the patients had symptoms startingwithin 12 hours after surfacing (85.4%),mainly within the first 3 hours and many had neurological manifestation (61.5%).Only 16.7% of the patients treated withHBOThad therapycommenced within 6 hours from the onset of symptomsand 93.8% from this group had complete recovery. Overall,76.0% of patients had fullrecovery after HBOT.
Conclusion:Diving activities must be closely monitored. Medical surveillance as well as legislations related to diving activities in Malaysia areessential to improve SCUBA discipline and to reduce mortality and morbidity ofDCI in the future.
Fulltext Perturbation of PI3K/Akt signaling affected autophagy modulation in dystrophin-deficient myoblasts

Yazid MD, Hung-Chih C

Cell Commun Signal, 2021 10 27;19(1):105.
PMID: 34706731 DOI: 10.1186/s12964-021-00785-0

BACKGROUND: The absence of dystrophin has gave a massive impact on myotube development in Muscular Dystrophy pathogenesis. One of the conserved signaling pathways involved in skeletal muscle differentiation is the PI3K/Akt/mTOR pathway that plays a vital role in autophagy regulation. To further understand and establish targeted therapy in dystrophin-deficient myoblasts, protein expression profiling has been determined which provides information on perturbed autophagy modulation and activation.
METHODS: In this study, a dystrophin-deficient myoblast cell line established from the skeletal muscle of a dystrophic (mdx) mouse was used as a model. The dfd13 (dystrophin-deficient) and C2C12 (non-dystrophic) myoblasts were cultured in low mitogen conditions for 10 days to induce differentiation. The cells were subjected to total protein extraction prior to Western blotting assay technique. Protein sub-fractionation has been conducted to determine protein localization. The live-cell analysis of autophagy assay was done using a flow cytometer.
RESULTS: In our culture system, the dfd13 myoblasts did not achieve terminal differentiation. PTEN expression was profoundly increased in dfd13 myoblasts throughout the differentiation day subsequently indicates perturbation of PI3K/Akt/mTOR regulation. In addition, rictor-mTORC2 was also found inactivated in this event. This occurrence has caused FoxO3 misregulation leads to higher activation of autophagy-related genes in dfd13 myoblasts. Autophagosome formation was increased as LC3B-I/II showed accumulation upon differentiation. However, the ratio of LC3B lipidation and autophagic flux were shown decreased which exhibited dystrophic features.
CONCLUSION: Perturbation of the PTEN-PI3K/Akt pathway triggers excessive autophagosome formation and subsequently reduced autophagic flux within dystrophin-deficient myoblasts where these findings are of importance to understand Duchenne Muscular Dystrophy (DMD) patients. We believe that some manipulation within its regulatory signaling reported in this study could help restore muscle homeostasis and attenuate disease progression. Video Abstract.
Fulltext Norepinephrine in Septic Shock: A Systematic Review and Meta-analysis

Ruslan MA, Baharuddin KA, Noor NM, Yazid MB, Noh AYM, Rahman A

West J Emerg Med, 2021 Feb 16;22(2):196-203.
PMID: 33856300 DOI: 10.5811/westjem.2020.10.47825

INTRODUCTION: Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.
METHODS: We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.
RESULTS: We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I2 = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I2 = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I2 = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I2 = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.
CONCLUSION: In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.
Fulltext Coatings in Decellularized Vascular Scaffolds for the Establishment of a Functional Endothelium: A Scoping Review of Vascular Graft Refinement

Heng JW, Yazid MD, Abdul Rahman MR, Sulaiman N

Front Cardiovasc Med, 2021;8:677588.
PMID: 34395554 DOI: 10.3389/fcvm.2021.677588

Developments in tissue engineering techniques have allowed for the creation of biocompatible, non-immunogenic alternative vascular grafts through the decellularization of existing tissues. With an ever-growing number of patients requiring life-saving vascular bypass grafting surgeries, the production of functional small diameter decellularized vascular scaffolds has never been more important. However, current implementations of small diameter decellularized vascular grafts face numerous clinical challenges attributed to premature graft failure as a consequence of common failure mechanisms such as acute thrombogenesis and intimal hyperplasia resulting from insufficient endothelial coverage on the graft lumen. This review summarizes some of the surface modifying coating agents currently used to improve the re-endothelialization efficiency and endothelial cell persistence in decellularized vascular scaffolds that could be applied in producing a better patency small diameter vascular graft. A comprehensive search yielding 192 publications was conducted in the PubMed, Scopus, Web of Science, and Ovid electronic databases. Careful screening and removal of unrelated publications and duplicate entries resulted in a total of 16 publications, which were discussed in this review. Selected publications demonstrate that the utilization of surface coating agents can induce endothelial cell adhesion, migration, and proliferation therefore leads to increased re-endothelialization efficiency. Unfortunately, the large variance in methodologies complicates comparison of coating effects between studies. Thus far, coating decellularized tissue gave encouraging results. These developments in re-endothelialization could be incorporated in the fabrication of functional, off-the-shelf alternative small diameter vascular scaffolds.
Fulltext The Intra- and Extra-Telomeric Role of TRF2 in the DNA Damage Response

Imran SAM, Yazid MD, Cui W, Lokanathan Y

Int J Mol Sci, 2021 Sep 14;22(18).
PMID: 34576063 DOI: 10.3390/ijms22189900

Telomere repeat binding factor 2 (TRF2) has a well-known function at the telomeres, which acts to protect the telomere end from being recognized as a DNA break or from unwanted recombination. This protection mechanism prevents DNA instability from mutation and subsequent severe diseases caused by the changes in DNA, such as cancer. Since TRF2 actively inhibits the DNA damage response factors from recognizing the telomere end as a DNA break, many more studies have also shown its interactions outside of the telomeres. However, very little has been discovered on the mechanisms involved in these interactions. This review aims to discuss the known function of TRF2 and its interaction with the DNA damage response (DDR) factors at both telomeric and non-telomeric regions. In this review, we will summarize recent progress and findings on the interactions between TRF2 and DDR factors at telomeres and outside of telomeres.
Fulltext Hydroxytyrosol Promotes Proliferation of Human Schwann Cells: An In Vitro Study

Kamil K, Yazid MD, Idrus RBH, Kumar J

Int J Environ Res Public Health, 2020 06 19;17(12).
PMID: 32575426 DOI: 10.3390/ijerph17124404

Recent advances in phytomedicine have explored some potential candidates for nerve regeneration, including hydroxytyrosol (HT). This study was undertaken to explore the potential effects of HT on human Schwann cells' proliferation. Methods: The primary human Schwann cell (hSC) was characterized, and the proliferation rate of hSC supplemented with various concentrations of HT was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis and protein expression of glial fibrillary acidic protein (GFAP) and p75 nerve growth factor receptor (p75 NGFR) were evaluated via the immunofluorescence technique. Results: In vitro culture of hSCs revealed spindle-like, bipolar morphology with the expression of specific markers of hSC. Hydroxytyrosol at 10 and 20 ng/mL significantly increased the proliferation of hSCs by 30.12 ± 5.9% and 47.8 ± 6.7% compared to control (p < 0.05). Cell cycle analysis showed that HT-treated hSCs have a higher proliferation index (16.2 ± 0.2%) than the control (12.4 ± 0.4%) (p < 0.01). In addition, HT significantly increased the protein expression of GFAP and p75NGFR (p < 0.05). Conclusion: HT stimulates the proliferation of hSCs in vitro, indicated by a significant increase in the hSC proliferation index and protein expression of hSCs' proliferation markers, namely p75 NGFR and GFAP.
Fulltext Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

Nordin A, Kamal H, Yazid MD, Saim A, Idrus R

BMC Complement Altern Med, 2019 Oct 30;19(1):290.
PMID: 31666058 DOI: 10.1186/s12906-019-2706-2

BACKGROUND: Nigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT.
METHODS: A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT.
RESULTS: A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone.
CONCLUSION: Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.
Post-impact disaster surveillance - a medical reconnaissance team at tsunami-struck sri lanka

Mohamad N, Abu Bakar NH, Mohamed NA, Baharudin KA, Noh AY, Ahmad R, et al.

Malays J Med Sci, 2007 Jan;14(1):79-83.
PMID: 22593659 MyJurnal

Emergency Medicine and Disaster Medicine are two specialties which are similar in the multidisciplinary involvement during the acute phase of the disaster. Recently, there was an increase in the number of disasters in the world but not many physicians are familiar with the principles for dealing with such situations, the unique organizational demands, coordination and the urgent need for medical assistance and relief. This case report delineates our experiences at a tsunami disaster area and the approach to setting up a medical relief team in the affected area. A medical reconnaissance team comprising of an emergency doctor from Hospital Universiti Sains Malaysia (H.U.S.M) and two MERCY Malaysia members was assembled. The team flew to Colombo on day 5 after the tsunami with medical supplies and related materials. The mission started from December 31(st) 2004 until January 8(th) 2005. Our surveillance area covered the Southern and Eastern Province with a total distance of 1700 km along the coast. The strategies employed during this medical reconnaissance included risk analysis, devising a resources matrix, developing lines of communication and rapport with other relief teams, Sri Lankan government agencies, and local and international non-government organizations. As a result, our team was able to set up a medical relief camp and distribute the relief items to the tsunami victims. In conclusion, the Disaster Emergency Medical Assistant Team (DEMAT) from H.U.S.M and MERCY Malaysia were able to set up and provide medical relief with our limited resources to a large scale disaster situation.
Fulltext The use of dental drill in removing entrapped finger by metal ring in emergency department

Shamsuddin SR, Hashim AA, Nazer B, Hashairi F, Shaik Farid AW, Abu Yazid MN

Med J Malaysia, 2012 Jun;67(3):349-50.
PMID: 23082436 MyJurnal

Ring removal is indicated in a number of clinical circumstances to manage or prevent tourniquet effect of the digit. A ring made from hardened metal may defy commonly known methods of removal. We reported a case of unusual difficulty in removing a ring of hardened metal composition using a dental drill. We believed the unusual circumstances of this case is likely to be repeated in some other clinical practice and this instrument is an appropriate option to consider in such cases.
Fulltext Differentiation analyses of adult suspension mononucleated peripheral blood cells of Mus musculus

Ariffin SH, Abidin IZ, Yazid MD, Wahab RM

Cell Commun Signal, 2010;8:29.
PMID: 20969794 DOI: 10.1186/1478-811X-8-29

The purpose of this study is to determine whether isolated suspension mouse peripheral mononucleated blood cells have the potential to differentiate into two distinct types of cells, i.e., osteoblasts and osteoclasts.
Fulltext Partial resection of pelvis and salvage of the lower limb in the treatment of malignant pelvic tumours

Faisham WI, Zulmi W, Aidura M, Yazid MD, Sallehuddin AY, Azman MZN, et al.

Med J Malaysia, 2001 Jun;56(2):248-51.
PMID: 11771089

Malignant pelvic tumours often present late, hence a high index of suspicion should be maintain in order to arrive at the diagnosis. This is particularly true for those who have unusual symptoms. A proper planning and staging strategies is required to save the limb, and the limb salvage surgery is at present the surgery of choice to achieve local control and restoring optimum functions of the lower limbs as being illustrated by our three cases.
Fulltext The Effects of Pro-Inflammatory and Anti-Inflammatory Agents for the Suppression of Intimal Hyperplasia: An Evidence-Based Review

Che Man R, Sulaiman N, Ishak MF, Bt Hj Idrus R, Abdul Rahman MR, Yazid MD

Int J Environ Res Public Health, 2020 10 26;17(21).
PMID: 33114632 DOI: 10.3390/ijerph17217825

Anti-atherogenic therapy is crucial in halting the progression of inflammation-induced intimal hyperplasia. The aim of this concise review was to methodically assess the recent findings of the different approaches, mainly on the recruitment of chemokines and/or cytokine and its effects in combating the intimal hyperplasia caused by various risk factors. Pubmed and Scopus databases were searched, followed by article selection based on pre-set inclusion and exclusion criteria. The combination of keywords used were monocyte chemoattractant protein-1 OR MCP-1 OR TNF-alpha OR TNF-α AND hyperplasia OR intimal hyperplasia OR neointimal hyperplasia AND in vitro. These keywords combination was incorporated in the study and had successfully identified 77 articles, with 22 articles were acquired from Pubmed, whereas 55 articles were obtained from Scopus. However, after title screening, only twelve articles meet the requirements of defined inclusion criteria. We classified the data into 4 different approaches, i.e., utilisation of natural product, genetic manipulation and protein inhibition, targeted drugs in clinical setting, and chemokine and cytokines induction. Most of the articles are working on genetic manipulation targeted on specific pathway to inhibit the pro-inflammatory factors expression. We also found that the utilisation of chemokine- and cytokine-related treatments are emerging throughout the years. However, there is no study utilising the combination of approaches that might give a better outcome in combating intimal hyperplasia. Hopefully, this concise review will provide an insight regarding the usage of different novel approaches in halting the progression of intimal hyperplasia, which serves as a key factor for the development of atherosclerosis in cardiovascular disease.
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 Molecular Action of Hydroxytyrosol in Attenuation of Intimal Hyperplasia: A Scoping Review

Vijakumaran U, Yazid MD, Hj Idrus RB, Abdul Rahman MR, Sulaiman N

Front Pharmacol, 2021;12:663266.
PMID: 34093194 DOI: 10.3389/fphar.2021.663266

Objective: Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation. Methods: A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria. Results: Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1β, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model. Conclusions: Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.
Fulltext Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review

Koh B, Sulaiman N, Fauzi MB, Law JX, Ng MH, Idrus RBH, et al.

Cell Biosci, 2020;10:75.
PMID: 32518618 DOI: 10.1186/s13578-020-00438-8

Stem cell-based regenerative medicine is a promising approach for tissue reconstruction. However, a large number of cells are needed in a typical clinical study, where conventional monolayer cultures might pose a limitation for scale-up. The purpose of this review was to systematically assess the application of microcarriers in Mesenchymal Stem Cell cultures. A comprehensive search was conducted in Medline via Ebscohost, Pubmed, and Scopus, and relevant studies published between 2015 and 2019 were selected. The literature search identified 53 related studies, but only 14 articles met the inclusion criteria. These include 7 utilised commercially available microcarriers, while the rest were formulated based on different surface characteristics, all of which are discussed in this review. Current applications of microcarriers were focused on MSC expansion and induction of MSCs into different lineages. These studies demonstrated that MSCs could proliferate in a microcarrier culture system in-fold compared to monolayer cultures, and the culture system could simulate a three-dimensional environment which induces cell differentiation. However, detailed studies are still required before this system were to be adapted into the scale of GMP manufacturing.
Fulltext Determination of the differentiation capacities of murines' primary mononucleated cells and MC3T3-E1 cells

Yazid MD, Ariffin SH, Senafi S, Razak MA, Wahab RM

Cancer Cell Int, 2010;10:42.
PMID: 20979664 DOI: 10.1186/1475-2867-10-42

The main morphological features of primitive cells, such as stem and progenitor cells, are that these cells consists only one nucleus. The main purpose of this study was to determine the differentiation capacities of stem and progenitor cells. This study was performed using mononucleated cells originated from murine peripheral blood and MC3T3-E1 cells. Three approaches were used to determine their differentiation capacities: 1) Biochemical assays, 2) Gene expression analysis, and 3) Morphological observations.
Oestrogen-induced epithelial-mesenchymal transition (EMT) in endometriosis: Aetiology of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome

Lih Yuan T, Sulaiman N, Nur Azurah AG, Maarof M, Rabiatul Adawiyah Razali, Yazid MD

Front Physiol, 2022;13:937988.
PMID: 36582359 DOI: 10.3389/fphys.2022.937988

Endometriosis occurs when endometrial-like tissue forms and grows outside the uterus due to oestrogen-induced epithelial-mesenchymal transition in the female reproductive tract. Factors that suppress this event could become potential therapeutic agents against disease occurrence and progression. However, an overview of these studies is still lacking. This review assessed the impact of a number factors on oestrogen-mediated epithelial-mesenchymal transition in the emergence of several diseases in the female reproductive tract, primarily endometriosis. The association between epithelial-mesenchymal transition and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome was also investigated. Oestrogen, Wnt4 and epithelial-mesenchymal transition were chosen as keywords in Scopus, PubMed, and Web of Science searches performed on 28th June 2021. Study selection was refined to cancer-irrelevant, English, original articles published between years 2011-2021. The full-text assessment was carried out for topic-related articles after title and abstract screening. Included studies were summarised and assessed for their risk of bias using the Office of Health Assessment and Translation tool. In this review, 10 articles investigating oestrogen and epithelial-mesenchymal transition in the female reproductive tract were summarised and classified into two groups: seven studies under 'factor'-modulated epithelial-mesenchymal transition and three studies under 'factor'-manipulated oestrogen-induced epithelial-mesenchymal transition. The current evidence proposes that epithelial-mesenchymal transition is one of the prime causes of reproductive-related disease. This event could be mediated by distinct stimuli, specifically oestrogen and Wnt4 aberration. The results of this review suggest that oestrogen and Wnt4 participate in epithelial-mesenchymal transition in vaginal epithelial cells in MRKH syndrome, adopting from the theories of endometriosis development, which could therefore serve as a foundation for novel target treatment, specifically related to vaginal epithelialisation, to ensure better surgical outcomes.
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 Peripheral Demyelinating Diseases: From Biology to Translational Medicine

Kamil K, Yazid MD, Idrus RBH, Das S, Kumar J

Front Neurol, 2019;10:87.
PMID: 30941082 DOI: 10.3389/fneur.2019.00087

Demyelinating diseases represent a spectrum of disorders that impose significant burden on global economy and society. Generally, the prognosis of these diseases is poor and there is no available cure. In recent decades, research has shed some light on the biology and physiology of Schwann cells and its neuroprotective effects in the peripheral nervous system (PNS). Insults to the PNS by various infectious agents, genetic predisposition and immune-related mechanisms jeopardize Schwann cell functions and cause demyelination. To date, there are no effective and reliable biomarkers for PNS-related diseases. Here, we aim to review the following: pathogenesis of various types of peripheral demyelinating diseases such as Guillain-Barre syndrome, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Anti-Myelin Associated Glycoprotein Neuropathy, POEMS syndrome, and Charcot-Marie-Tooth disease; emerging novel biomarkers for peripheral demyelinating diseases, and Schwann cell associated markers for demyelination.

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