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Retrospective analysis of results of treatment for nasopharyngeal carcinoma in Penang General Hospital from 2001-2005

Phua CE, Tan BS, Yong TK, Govindasamy M

Asian Pac J Cancer Prev, 2011;12(12):3197-200.
PMID: 22471453

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the commonest cancers encountered in Malaysia. This study aimed to evaluate the treatment outcomes for patients with NPC treated in Penang General Hospital with specific analysis of prognostic clinicopathological features and treatment modalities.
MATERIALS AND METHODS: This retrospective study examined NPC patients between 1st January 2001 and 31st December 2005 in Penang General Hospital. Survival analyses were performed using the Kaplan-Meier method and comparisons between groups were made using the log-rank test. Important prognostic factors including patient demographics, tumour and treatment factors were analysed using the Cox proportional hazard model.
RESULTS: A total of 285 patients were identified with a median age of 51 years, 72.6% being males. The majority were Chinese (66%) followed by Malays (31.9%). Primary tumour stages (T stages) 3 and 4 were present in 18.6% and 34% of patients respectively, and nodal disease was present in 80.4%. On overall AJCC staging, 29.1% had stage III and 50.2% had stage IV disease. Some 39.6% of patients had WHO type 3 histology and 7.4% had WHO type 1-2 histology with the remainder having NPC with no subtype reported. Concurrent chemo-irradiation was the commonest treatment received by patients (51.9%) followed by radiotherapy alone (41.8%). The 5 year overall survival and cause specific survival were 33.3% and 42.7% respectively. Age group, T stage, N stage and WHO histological subtype were independent prognostic factors for overall survival on multivariate analysis. For cause specific survival they were T stage and N stage.
CONCLUSION: The 5 years overall survival rate was 33.3%. This low figure is primarily due to late presentation. Efforts to detect NPC at earlier stages in Malaysia are urgently needed. These should include public education to increase awareness of the prevalence of this highly treatable disease.
Fulltext Retinal vasculitis in systemic lupus erythematosus: an indication of active disease

Md Noh UK, Zahidin AZ, Yong TK

Clin Pract, 2012 Mar 30;2(2):e54.
PMID: 24765453 DOI: 10.4081/cp.2012.e54

A 26-year-old woman with a recent flare-up of systemic lupus erythematosus presented with peripheral retinal hemorrhages at a routine check-up. She is on a tapering dose of immunosuppressive agents. Her visual acuity was good. Fluorescein angiogram revealed vasculitic changes with capillary non-perfusion areas. A few weeks later, she developed cerebral lupus with advanced lupus nephritis. Immunosuppressive therapy was restarted and panretinal photocoagulation was delivered. Her visual acuity remained stable, despite development of a cataract from prednisolone therapy.
Understanding the multifaceted mechanisms of diabetic wound healing and therapeutic application of stem cells conditioned medium in the healing process

Fui LW, Lok MPW, Govindasamy V, Yong TK, Lek TK, Das AK

J Tissue Eng Regen Med, 2019 12;13(12):2218-2233.
PMID: 31648415 DOI: 10.1002/term.2966

Mesenchymal stem cells (MSCs) transplantation seems to be a promising new therapy for diabetic wound healing (DWH), and currently, arrays of MSCs from various sources ranging from umbilical, adipose to dental sources are available as a treatment modality for this disease. However, it now appears that only a fraction of transplanted cells actually assimilate and survive in host tissues suggesting that the major mechanism by which stem cells participate in tissue repair are most likely related to their secretome level. These include a wide range of growth factors, cytokines, and chemokines, which can be found from the conditioned medium (CM) used to culture the cells. Basic studies and preclinical work confirm that the therapeutic effect of CMs are comparable with the application of stem cells. This review describes in detail the wound healing process in diabetes and the cellular and biological factors that influence the process. Subsequently, through a comprehensive literature search of studies related to wound healing in diabetics, we aim to provide an overview of scientific merits of using MSCs-CM in the treatment of diabetic wound as well as the significant caveats, which restricts its potential use in clinical set-ups. To our best knowledge, this is one of the first review papers that collect the importance of stem cells as an alternative treatment to the DWH. We anticipate that the success of this treatment will have a significant clinical impact on diabetic wounds.
Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy

Sun Y, Lu Y, Li X, He Y, Yong TK, Keng CS, et al.

Cell Death Dis, 2024 Aug 28;15(8):632.
PMID: 39198434 DOI: 10.1038/s41419-024-07008-7

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple "wisdom" by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.
Corneal regeneration by induced human buccal mucosa cultivated on an amniotic membrane following alkaline injury

Man RC, Yong TK, Hwei NM, Halim WHWA, Zahidin AZM, Ramli R, et al.

Mol Vis, 2017;23:810-822.
PMID: 29225457

Various clinical disorders and injuries, such as chemical, thermal, or mechanical injuries, may lead to corneal loss that results in blindness. PURPOSE: The aims of this study were to differentiate human buccal mucosa (BMuc) into corneal epithelial-like cells, to fabricate engineered corneal tissue using buccal mucosal epithelial cells, and to reconstruct a damaged corneal epithelium in a nude rat model.
Methods: BMuc were subjected to 10 d of induction factors to investigate the potential of cells to differentiate into corneal lineages.
Results: Corneal stem cell markers β1-integrin, C/EBPδ, ABCG2, p63, and CK3 were upregulated in the gene expression analysis in induced BMuc, whereas CK3 and p63 showed significant protein expression in induced BMuc compared to the uninduced cells. BMuc were then left to reach 80% confluency after differential trypsinization. The cells were harvested and cultivated on a commercially available untreated air-dried amniotic membrane (AM) in a Transwell system in induction medium. The corneal constructs were fabricated and then implanted into damaged rat corneas for up to 8 weeks. A significant improvement was detected in the treatment group at 8 weeks post-implantation, as revealed by slit lamp biomicroscopy analysis. The structure and thickness of the corneal layer were also analyzed using histological staining and time-domain optical coherence tomography scans and were found to resemble a native corneal layer. The protein expression for CK3 and p63 were continuously detected throughout the corneal epithelial layer in the corneal construct.
Conclusions: In conclusion, human BMuc can be induced to express a corneal epithelial-like phenotype. The addition of BMuc improves corneal clarity, prevents vascularization, increases corneal thickness and stromal alignment, and appears to have no adverse effect on the host after implantation.
Low-temperature synthesis of indium tin oxide nanowires as the transparent electrodes for organic light emitting devices

Kee YY, Tan SS, Yong TK, Nee CH, Yap SS, Tou TY, et al.

Nanotechnology, 2012 Jan 20;23(2):025706.
PMID: 22166812 DOI: 10.1088/0957-4484/23/2/025706

Low-temperature growth of indium tin oxide (ITO) nanowires (NWs) was obtained on catalyst-free amorphous glass substrates at 250 °C by Nd:YAG pulsed-laser deposition. These ITO NWs have branching morphology as grown in Ar ambient. As suggested by scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM), our ITO NWs have the tendency to grow vertically outward from the substrate surface, with the (400) plane parallel to the longitudinal axis of the nanowires. These NWs are low in electrical resistivity (1.6×10⁻⁴ Ω cm) and high in visible transmittance (~90–96%), and were tested as the electrode for organic light emitting devices (OLEDs). An enhanced current density of ~30 mA cm⁻² was detected at bias voltages of ~19–21 V with uniform and bright emission. We found that the Hall mobility of these NWs is 2.2–2.7 times higher than that of ITO film, which can be explained by the reduction of Coulomb scattering loss. These results suggested that ITO nanowires are promising for applications in optoelectronic devices including OLED, touch screen displays, and photovoltaic solar cells.
Fulltext Human Dental Pulp Stem Cells (DPSCs) Therapy in Rescuing Photoreceptors and Establishing a Sodium Iodate-Induced Retinal Degeneration Rat Model

Lam C, Alsaeedi HA, Koh AE, Harun MHN, Hwei ANM, Mok PL, et al.

Tissue Eng Regen Med, 2021 02;18(1):143-154.
PMID: 33415670 DOI: 10.1007/s13770-020-00312-1

BACKGROUND: Different methods have been used to inject stem cells into the eye for research. We previously explored the intravitreal route. Here, we investigate the efficacy of intravenous and subretinal-transplanted human dental pulp stem cells (DPSCs) in rescuing the photoreceptors of a sodium iodate-induced retinal degeneration model.
METHODS: Three groups of Sprague Dawley rats were used: intervention, vehicle group and negative control groups (n = 6 in each). Intravenous injection of 60 mg/kg sodium iodate (day 0) induced retinal degeneration. On day 4 post-injection of sodium iodate, the rats in the intervention group received intravenous DPSC and subretinal DPSC in the right eye; rats in the vehicle group received subretinal Hank's balance salt solution and intravenous normal saline; while negative control group received nothing. Electroretinogram (ERG) was performed to assess the retinal function at day 0 (baseline), day 4, day 11, day 18, day 26, and day 32. By the end of the study at day 32, the rats were euthanized, and both their enucleated eyes were sent for histology.
RESULTS: No significant difference in maximal ERG a-wave (p = 0.107) and b-wave, (p = 0.153) amplitude was seen amongst the experimental groups. However, photopic 30 Hz flicker amplitude of the study eye showed significant differences in the 3 groups (p = 0.032). Within the intervention group, there was an improvement in 30 Hz flicker ERG response of all 6 treated right eyes, which was injected with subretinal DPSC; while the 30 Hz flicker ERG of the non-treated left eyes remained flat. Histology showed improved outer nuclear layer thickness in intervention group; however, findings were not significant compared to the negative and vehicle groups.
CONCLUSION: Combination of subretinal and intravenous injection of DPSCs may have potential to rescue cone function from a NaIO3-induced retinal injury model.
Physicochemical and thermal characteristics of choline chloride-based deep eutectic solvents

Sazali AL, AlMasoud N, Amran SK, Alomar TS, Pa'ee KF, El-Bahy ZM, et al.

Chemosphere, 2023 Oct;338:139485.
PMID: 37442394 DOI: 10.1016/j.chemosphere.2023.139485

It is essential to investigate the physicochemical and thermal properties of choline chloride (ChCl)-based deep eutectic solvents (DESs) as hydrogen bond acceptor (HBA) with various hydrogen bond donor (HBD) functional groups, such as α-hydroxy acid (lactic acid) or polyol (glycerol). It is important to consider how molar ratios impact these properties, as they may be altered for particular applications. This study aimed to examine the physicochemical and thermal properties of ChCl-based DESs with lactic acid (LA) or glycerol (Gly) at different molar ratios (1:2-1:10). The pH of ChCl:LA (0-1.0) is lower than that of ChCl:Gly (4.0-5.0) because of the hydrogen bonds between ChCl and LA. A higher amount of LA/Gly resulted in higher densities of ChCl:Gly (1.20-1.22 g cm-3) and ChCl:LA (1.16-1.19 g cm-3) due to the stronger hydrogen bonds and tighter packing of the molecules. The refractive index of ChCl:Gly (1.47-1.48) was higher than ChCl:LA (1.44-1.46), with a trend similar to density. The viscosities of ChCl:Gly (0.235-0.453 Pa s) and ChCl:LA (0.04-0.06 Pa s) increased with increasing LA/Gly molar ratio but decreased with temperature due to the high kinetic energy from heating, lowering the attractive forces between molecules. The activation energy for ChCl:LA (15.29-15.55 kJ mol-1) is greater than for ChCl:Gly (7.77-8.78 kJ mol-1), indicating that ChCl:LA has a greater viscosity-temperature dependence than ChCl:Gly. The DESs decomposition temperatures are 179.73-192.14 °C for ChCl:LA and 189.69-197.41 °C for ChCl:Gly. Freezing temperatures are correlated with the molecular weight of HBDs, with lower values causing a larger decrease in freezing temperatures. The interactions of polyols with anions were stronger than those of α-hydroxy acids with anions. The variations in HBA to HBD molar ratios affected DESs properties, providing a fundamental understanding of the properties critical for their diverse applications.
A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society

Tsubota K, Yokoi N, Watanabe H, Dogru M, Kojima T, Yamada M, et al.

Eye Contact Lens, 2020 Jan;46 Suppl 1:S2-S13.
PMID: 31425351 DOI: 10.1097/ICL.0000000000000643

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.