MyMedR

Displaying all 8 publications

Abstract:

Sort:

Fulltext Cardiac Stem Cells for Myocardial Regeneration: They Are Not Alone

Leong YY, Ng WH, Ellison-Hughes GM, Tan JJ

Front Cardiovasc Med, 2017;4:47.
PMID: 28770214 DOI: 10.3389/fcvm.2017.00047

Heart failure is the number one killer worldwide with ~50% of patients dying within 5 years of prognosis. The discovery of stem cells, which are capable of repairing the damaged portion of the heart, has created a field of cardiac regenerative medicine, which explores various types of stem cells, either autologous or endogenous, in the hope of finding the "holy grail" stem cell candidate to slow down and reverse the disease progression. However, there are many challenges that need to be overcome in the search of such a cell candidate. The ideal cells have to survive the harsh infarcted environment, retain their phenotype upon administration, and engraft and be activated to initiate repair and regeneration in vivo. Early bench and bedside experiments mostly focused on bone marrow-derived cells; however, heart regeneration requires multiple coordinations and interactions between various cell types and the extracellular matrix to form new cardiomyocytes and vasculature. There is an observed trend that when more than one cell is coadministered and cotransplanted into infarcted animal models the degree of regeneration is enhanced, when compared to single-cell administration. This review focuses on stem cell candidates, which have also been tested in human trials, and summarizes findings that explore the interactions between various stem cells in heart regenerative therapy.
Providing End-of-Life Care in the Community: What Are the Challenges in Malaysia?

Leong YY, Hamzah E, McCarthy S, Lim ZN

J Hosp Palliat Care, 2022 Sep 01;25(3):133-137.
PMID: 37674906 DOI: 10.14475/jhpc.2022.25.3.133

A 72-year-old woman with metastatic lung cancer to bone and brain and with left external iliac vein thrombosis was under the care of a community palliative care provider. She experienced an acute pain crisis due to acute limb ischemia of the left lower limb. Goals-of-care discussions were held with the patient and her family; she prioritized symptom control and end-of-life care at home. The family and patient were aware of her short prognosis. Her complex pain was managed by the community palliative team, and her family was empowered to give subcutaneous injections. We illustrate a case showing the importance of community health services with palliative care support in providing symptom management and support to patient and family caregivers throughout the course of a life-limiting illness. It also highlights family caregivers' potential psychological distress in delivering subcutaneous injections in terminal care for a patient at home.
Sonographic nomogram of paediatric renal size in Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)

Leong YY, Kanaheswari Y, Faizah MZ, Hing EY, Nik Ismail NA, Nik Fuad NF, et al.

Med J Malaysia, 2020 03;75(2):130-135.
PMID: 32281593

INTRODUCTION: A person's childhood is an important period of growth, and also one's most vulnerable, as one can be exposed to various pathologies, for example those that could affect the growth of one's kidney. Asians are physiologically different from Caucasians, and the nomogram renal size obtained from a Western population (mostly of Caucasians) is not be suitable for representing Asian children. As such a nomogram on paediatric renal size derived from Malaysia is needed.
METHODS: A total of 109 (64 males and 45 females) aged 0-12 in Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) took part in this study. They underwent ultrasonography of both kidneys, and their demographic and anthropometric data were collected. The mean and standard deviations of the renal length and renal volume according to their age groups was calculated, and the final data was compared to the ones reported by Rosenbaum et al. (1984).
RESULT: Body weight and Body Surface Area (BSA) of the children reported the strongest correlation with renal size. Significant differences were found between local and the data from Rosenbaum et al (1984). A nomogram on paediatric renal size based on children in PPUKM was then created.
DISCUSSION: Ultrasonography is regarded as the standard method for determining renal size. Body weight and BSA were both strongly correlated with renal size. It was shown that the widely used nomograms derived from data obtained from Caucasian was not suitable to represent the population of Malaysian children.
Success Rate of Adrenal Venous Sampling and its Determining Factors: Experience of a Single Center in Malaysia

Muhamad Pauzi KN, Zakaria R, Leong YY, Nik Fuad NF, Nik Ismail NA, Sukor N

Ann Vasc Surg, 2024 Jan;98:258-267.
PMID: 37820987 DOI: 10.1016/j.avsg.2023.08.021

BACKGROUND: Primary hyperaldosteronism has been regarded as the commonest and potentially curable cause of secondary hypertension in up to 80% of cases if this condition is detected early. Laparoscopic adrenalectomy proved to be a promising curable method for primary hyperaldosteronism secondary to aldosterone producing adenoma, while primary hyperaldosteronism secondary to bilateral adrenal hyperplasia requires optimization of medical treatment. Adrenal venous sampling (AVS) has been recommended by the Endocrine Society's guideline in addressing the subtypes of primary hyperaldosteronism. Therefore, determining success rate of AVS in our center is crucial in the management of primary hyperaldosteronism and to prevent redundant procedures. The objectives of this study were to evaluate the success rate of AVS in our center and the associated factors that correlate with the success rate.
METHODS: A retrospective study in a single center, all adult patients who were diagnosed with primary hyperaldosteronism and underwent AVS in our center between 2014 until 2022 were included. Successful samples defined by a selectivity index of ≥2, that is, the ratio of adrenal vein cortisol level to the peripheral vein cortisol level, were evaluated. The baseline demographic characteristics of each patient, technical parameters of AVS, and anatomical parameters of right adrenal vein from the venographic images were evaluated and analyzed to correlate with the outcome of AVS. A P-value of <0.05 was considered statistically significant.
RESULTS: The overall success rate of AVS in our center was 61.3%. The success rate significantly increased to 80.6% in the trained interventional radiologist (IR) group, which represents a single IR who had completed specific training in AVS, compared to non-trained IR group which consisted of a total of 10 IRs without specific AVS training (P = 0.046). The right AVS had lower success rate than the left AVS (64% vs. 94.6%). The type of right adrenal vein pattern showed significant association with the outcome of AVS (P = 0.014). There were 6 types of right adrenal vein patterns observed in our study; Type 1 - gland-like pattern with numerous branches, Type 2 - delta pattern, Type 3 - triangular pattern with central "blush", Type 4 - no discernible pattern and Type 5 - spidery or stellate pattern. The sixth pattern was the hepatic radicles blush with hepatic drainage, for which blood sampling were also collected due to its appearance was frequently indistinguishable from the Type 1 pattern. The results showed Type 2 pattern had the highest incidence (30.5%; 32/105 samples) and Type 5 had the highest success rate (100%; 11/11 samples), while the hepatic radicles blush pattern had the highest incidence in fail samples resulting in the highest failure rate (94.7%; 18/19 samples). The visualization of the inferior emissary vein (IEV) from the venographic images during right AVS had a significant association with the successful AVS (97.5% success rate; 39/40 samples; P = 0.003). Contrariwise, blood sampling withdrawn from the right adrenal vein in the presence of hepatic drainage communication associated with the failure AVS (86.7% failure rate; 26/30 samples; P = 0.001).
CONCLUSIONS: The overall success rate of both AVS in our center was 61.3%, and the success rate was higher in the trained IR group than the non-trained IR group. The visualization of IEV and the type of right adrenal vein patterns were the key determining factors with significant association to the successful right AVS. Conversely, blood sampling withdrawn from the hepatic radicles and hepatic drainage had significant association with the failure right AVS.
Human mesenchymal stem cells promote CD34+hematopoietic stem cell proliferation with preserved red blood cell differentiation capacity

Lau SX, Leong YY, Ng WH, Ng AWP, Ismail IS, Yusoff NM, et al.

Cell Biol Int, 2017 Jun;41(6):697-704.
PMID: 28403524 DOI: 10.1002/cbin.10774

Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord blood-derived CD34+hematopoietic stem cells (HSCs) offered greater therapeutic effects but little is known regarding the effects of human Wharton's jelly derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This study aimed to investigate the effects of MSCs on HSC expansion and differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived conditioned medium, with HSCs cultured under standard medium served as a control. Cell expansion rates, number of mononuclear cell post-expansion and number of enucleated cells post-differentiation were evaluated. HSCs showed superior proliferation in the presence of MSC with mean expansion rate of 3.5 × 108 ± 1.8 × 107after day 7 compared to the conditioned medium and the control group (8.9 × 107 ± 1.1 × 108and 7.0 × 107 ± 3.3 × 106respectively, P
Guided evaluation and standardisation of mesenchymal stem cell culture conditions to generate conditioned medium favourable to cardiac c-kit cell growth

Ng WH, Umar Fuaad MZ, Azmi SM, Leong YY, Yong YK, Ng AMH, et al.

Cell Tissue Res, 2019 Feb;375(2):383-396.
PMID: 30232595 DOI: 10.1007/s00441-018-2918-7

Mesenchymal stem cells (MSCs) are known to secrete cardioprotective paracrine factors that can potentially activate endogenous cardiac c-kit cells (CCs). This study aims to optimise MSC growth conditions and medium formulation for generating the conditioned medium (CdM) to facilitate CC growth and expansion in vitro. The quality of MSC-CdM after optimisation of seeding density during MSC stabilisation and medium formulation used during MSC stimulation including glucose, ascorbic acid, serum and oxygen levels and the effects of treatment concentration and repeated CdM harvesting were assessed based on CC viability in vitro under growth factor- and serum-deprived condition. Our data showed that functional CdM can be produced from MSCs with a density of 20,000 cells/cm2, which were stimulated using high glucose (25 mM), ascorbic acid supplemented, serum-free medium under normoxic condition. The generated CdM, when applied to growth factor- and serum-deprived medium at 1:1 ratio, improved CC viability, migration and proliferation in vitro. Such an effect could further be augmented by generating CdM concentrates without compromising CC gene and protein expressions, while retaining its capability to undergo differentiation to form endothelial, smooth muscle and cardiomyocytes. Nevertheless, CdM could not be repeatedly harvested from the same MSC culture, as the protein content and its effect on CC viability deteriorated after the first harvest. In conclusion, this study provides a proof-of-concept strategy to standardise the production of CdM from MSCs based on rapid, stepwise assessment of CC viability, thus enabling production of CdM favourable to CC growth for in vitro or clinical applications.
Mesenchymal stem cells facilitate cardiac differentiation in Sox2-expressing cardiac C-kit cells in coculture

Leong YY, Ng WH, Umar Fuaad MZ, Ng CT, Ramasamy R, Lim V, et al.

J Cell Biochem, 2019 06;120(6):9104-9116.
PMID: 30548289 DOI: 10.1002/jcb.28186

Stem cell therapy offers hope to reconstitute injured myocardium and salvage heart from failing. A recent approach using combinations of derived Cardiac-derived c-kit expressing cells (CCs) and mesenchymal stem cells (MSCs) in transplantation improved infarcted hearts with a greater functional outcome, but the effects of MSCs on CCs remain to be elucidated. We used a novel two-step protocol to clonogenically amplify colony forming c-kit expressing cells from 4- to 6-week-old C57BL/6N mice. This method yielded highly proliferative and clonogenic CCs with an average population doubling time of 17.2 ± 0.2, of which 80% were at the G1 phase. We identified two distinctly different CC populations based on its Sox2 expression, which was found to inversely related to their nkx2.5 and gata4 expression. To study CCs after MSC coculture, we developed micron-sized particles of iron oxide-based magnetic reisolation method to separate CCs from MSCs for subsequent analysis. Through validation using the sex and species mismatch CC-MSC coculture method, we confirmed that the purity of the reisolated cells was greater than 85%. In coculture experiment, we found that MSCs prominently enhanced Ctni and Mef2c expressions in Sox2 pos CCs after the induction of cardiac differentiation, and the level was higher than that of conditioned medium Sox2 pos CCs. However, these effects were not found in Sox2 neg CCs. Immunofluorescence labeling confirmed the presence of cardiac-like cells within Sox2 pos CCs after differentiation, identified by its cardiac troponin I and α-sarcomeric actinin expressions. In conclusion, this study shows that MSCs enhance CC differentiation toward cardiac myocytes. This enhancement is dependent on CC stemness state, which is determined by Sox2 expression.
Incidence and risk factors of symptomatic dry eye disease in Asian Malays from the Singapore Malay Eye Study

Man REK, Veerappan AR, Tan SP, Fenwick EK, Sabanayagam C, Chua J, et al.

Ocul Surf, 2017 Oct;15(4):742-748.
PMID: 28442380 DOI: 10.1016/j.jtos.2017.04.004

PURPOSE: To evaluate the incidence of symptomatic dry eye disease (SDED) and associated risk factors in a well-characterized cohort of ethnic Malays in Singapore.

METHODS: We included 1682 participants (mean age [SD]: 57 [10]years; 55.4% female) without SDED from the Singapore Malay Eye Study (SiMES), a population-based longitudinal study with baseline examination (SiMES-1) conducted between 2004 and 2006, and follow-up examination (SiMES-2) conducted between 2010 and 2013. SDED was considered to be present if a participant answered "often" or "all the time" to any of the six questions from the Salisbury Eye Evaluation Study dry eye questionnaire. Age-standardized incidence of SDED was calculated as the crude 6-year cumulative incidence standardized to Singapore's population census. Gender-stratified multivariable log-binomial regression models were utilized to determine the independent risk factors of incident SDED.

RESULTS: At the 6-year follow-up, 86 of 1682 participants had developed SDED, which was equivalent to an age-standardized 6-year incidence of 5.1% (95% CI 4.1-6.4%). There were no differences in the incidence of SDED between men and women (P = 0.9). Multivariable models revealed that presence of glaucoma and poorer self-rated health were independently associated with incident SDED in men (P = 0.003 and 0.03, respectively), while contact lens wear (P = 0.002), history of thyroid disease (P = 0.03), and having had cataract surgery (P = 0.02) were predictive of incident SDED in women.

CONCLUSION: One in twenty adult Malays developed SDED over a 6-year period. Risk factors for incident SDED were different between men and women. Future studies and public health interventions should consider this gender-specific difference in risk factors.