Current Progress in Tendon and Ligament Tissue Engineering

Wei Lee Lim,Ling Ling Liau,Min Hwei Ng,Shiplu Roy Chowdhury,Jia Xian Law 한국조직공학과 재생의학회 2019 조직공학과 재생의학 Vol.16 No.6

BACKGROUND: Tendon and ligament injuries accounted for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year and thus imposed a significant burden to the society and the economy. Damaged tendon and ligament can severely affect the normal body movement and might lead to many complications if not treated promptly and adequately. Current conventional treatment through surgical repair and tissue graft are ineffective with a high rate of recurrence. METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament. RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro. CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.

Flexural Behaviour of Reinforced Lightweight Foamed Mortar Beams and Slabs

Yee Ling Lee,Jee Hock Lim,Siong Kang Lim,Cher Siang Tan 대한토목학회 2018 KSCE JOURNAL OF CIVIL ENGINEERING Vol.22 No.8

This paper presents the experimental results on flexural behaviour of reinforced concrete beams and slabs made of lightweightfoamed mortar with density ranged from 1700 to 1800 kg/m3. Beam specimens consist of seven lightweight foamed mortar beamsand three normal weight concrete beams acted as the control sample. Whereas, slab specimens contain two lightweight foamedmortar slabs and two normal weight concrete slabs. Four types of lightweight foamed mortar with different cement-sand ratios andwater-cement ratios designated as LW-1, LW-2, LW-3 and LW-4 were produced in order to achieve targeted compressive strength of20 MPa at 28 days for structural usage. The results showed that reinforced lightweight foamed mortar beams sustained about 8% to34% lower ultimate load as compared to normal weight reinforced concrete with same reinforcement configuration. However,lightweight foamed mortar slab sustained higher ultimate load, averagely 18% as compared to normal weight slab. Apart from that, itwas observed that the both reinforced lightweight foamed mortar beams and slabs were weak in resisting shear forces nonethelessflexural failure cannot be ignored entirely due to the presence of excessive yielding of the steel strain data.

Inhibition of VLA-4/VCAM-1-mediated Cell Adhesion by Triterpenoid Saponins from Bupleurum falcatum L

Lee, Seung-Woong,Kim, Min-Seok,Lim, Ju-Hwan,Chang, Jong-Sun,Ling, Jin,Bae, Ki-Hwan,Lee, Woo-Song,Rho, Mun-Chual Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.7

Discovery and isolation of compounds capable of blocking the interactions between VCAM-1 and VLA-4, a major pair of adhesion molecules contributing to the different steps of leukocyte migration across the endothelium in inflammatory responses, has been a major goal of this lab. Through bioactivity-guided fractionation, five saikosaponins were subsequently isolated from the methanol extracts of the roots of Bupleurum falcatum L. Their structures were elucidated by spectroscopic analysis ($^1H-$, $^{13}C$-NMR and 2D-NMR), as follows, saikosaponins: A (1); D (2); C (3); B3 (4); B4 (5). Compounds 1 and 2 inhibited interaction of sVCAM-1 and VLA-4 of THP-1 cells with respective $IC_{50}$ values of 7.8 and 1.7 ${\mu}M$. The aglycone structure of 2 also showed cell adhesion inhibitory activity with an $IC_{50}$ value of 21.1 ${\mu}M$. With these results, we suspect these two saikosaponins from the Bupleurum falcatum L. roots to be prime candidates for therapeutic strategies towards inflammation.

Fabrication of polarization-insensitive, multi-resonant metamaterial absorber using wafer bonding of glass dielectric substrate

Lee, Duck-Hyun,Ling, Kenyu,Lim, Sungjoon,Baek, Chang-Wook Elsevier 2015 MICROELECTRONIC ENGINEERING Vol.136 No.-

<P><B>Abstract</B></P> <P>We present the design, fabrication and characterization of a terahertz multi-resonant metamaterial absorber showing polarization-insensitive characteristics. The proposed absorber uses Pyrex glass as a dielectric layer for higher absorption in a terahertz range and is wafer-level fabricated by thermo-compression bonding technique using gold films as intermediate layers. In addition, an array of comb-shaped hexagonal pattern is introduced as a multi-band LC resonator and symmetric geometry is used for polarization insensitivity. The fabricated absorber shows two absorption peaks at 0.98THz and 1.55THz with the absorptivity of 93% and 74%, respectively, and almost identical responses to the different polarization angles.</P> <P><B>Highlights</B></P> <P> <UL> <LI> THz multi-resonant metamaterial absorber using glass wafer bonding is demonstrated. </LI> <LI> Pyrex glass wafer is used as a dielectric layer for high absorptivity in THz range. </LI> <LI> Hexagonal comb-shape resonator is used to realize polarization insensitivity. </LI> <LI> Fabricated absorber shows an absorptivity of 93% and 74%, at 0.98THz and 1.55THz. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Technology readiness trait – does it has a role to accelerate patient’s adoption of e-health?

LEE Wan Ling,LIM Zi Jing 한국간호과학회 2021 한국간호과학회 학술대회 Vol.2021 No.10

Aim(s): The COVID-19 pandemic has catalysed the digital transformation of healthcare but the extent to which patients are ready to adopt e-health is yet to be determined, including middle-income countries. Among the many patient determinants of e-health being studied, an innate trait called “technology readiness” is underexplored in clinical research. Study aimed to examine the role patient’s technology readiness (TR) in relation to e-health literacy (eHL) that influence e-health adoption Method(s): A cross-sectional survey was conducted in a tertiary hospital in Malaysia. A total of 276 adult in-patients with hypertension, diabetic mellitus and coronary heart disease had completed eHealth Literacy Scale, Technology Readiness Index (2.0), behaviour and perceived use of digital technology in addressing health problem. Hierarchical linear regression analysis using entry block was performed to examine the effects of the four subdomains of TR on eHL after controlling for other independent variables. Result(s): Patients had moderate TR (mean =3.03). Regression model shows TR is a strong determinant of eHL (Δ R2 =.295, P<.001) with its subdomains (optimism, innovativeness and discomfort) significantly influencing eHL (|β| = 0.28-0.40; P values < 0.001), except for the subdomain insecurity. Among the 97.1 % of patients owning the smartphone, about 24% and 12% used mobile health apps and fitness devices, respectively. The low 22% patients read health-related materials presents a concern in view that digital materials are often heavily textual. Conclusion(s): The deployment of digital health interventions should incorporate assessment of patients’ TR for targeted strategies. Design and delivery of technology-based interventions that are tailored to patient’s TR will enhance better patient engagement and adoption of e-health.

Improvement of Bone Mineral Density and Markers of Proximal Renal Tubular Function in Chronic Hepatitis B Patients Switched from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide

( Tse-ling Fong ),( Brian Lee ),( Andy Tien ),( Mimi Chang ),( Carolina Lim ),( Ho S. Bae ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Tenofovir alafenamide (TAF) is a novel prodrug that re-duces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF. Methods: This was a prospective single-arm open-label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA < 21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Results: BMD significantly increased after switch from TDF to TAF from baseline to week 12 and remained stable at week 24. Mean percent changes from baseline to week 12 in hip and spine BMDs significantly increased (+ 12.9% and +2.4%, respectively). There were significantly more patients with gains in hip (86%) or spine (76%) BMD than patients who experienced loss (11% and 25%, respectively). No significant change in BMD was seen between week 12 and 24. There was no significant difference in eGFR_CG from baseline to week 24. Significant improvement was observed in urinary beta-2 micro globulin/creatinine ratio between baseline and week 12 that remained through week 24 (median change from baseline to week 12 and 24; 1.5, 1.0 and 1.1 mcg/g respectively; P<0.01). Similar changes were observed with retinol binding protein/creatinine ratio at from baseline to week 12 and 24 (median change from baseline to week 12 and 24; 1.7, 1.3 and 1.4 mcg/g respectively; P<0.01). There was significant increase in fractional excretion of phosphate from baseline to week 24 (11.9 to 14.0; P<0.05). Phosphate threshold for renal tubular reabsorption decreased from baseline to week 12 (2.8 to 2.6 mg/dL). Conclusions: Switching from long-term TDF to TAF among CHB patients was associated with significant improvement in BMD and some markers of proximal renal tubular function. There was no improvement in urinary phosphate handling after the switch which suggests TDF has a direct effect on bone metabolism that is reversible. Longer term and larger studies are needed to confirm these findings.

The inhibitory effect of pyrogallol on tyrosinase activity and structure: Integration study of inhibition kinetics with molecular dynamics simulation

Xiong, Shang-Ling,Lim, Gyu Tae,Yin, Shang-Jun,Lee, Jinhyuk,Si, Yue-Xiu,Yang, Jun-Mo,Park, Yong-Doo,Qian, Guo-Ying Elsevier 2019 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.121 No.-

<P><B>Abstract</B></P> <P>Pyrogallol is naturally found in aquatic plant and has been proposed as a substrate of tyrosinase. In this study, we evaluated the dual effect of pyrogallol on tyrosinase as an inhibitor in the presence of L‑DOPA simultaneously via integrating methods of enzyme kinetics and computational molecular dynamics (MD) simulations. Pyrogallol was found to be a reversible inhibitor of tyrosinase in the presence of L‑DOPA and its induced mechanism was the parabolic non-competitive inhibition type (<I>IC</I> <SUB>50</SUB> = 0.772 ± 0.003 mM and <I>K</I> <SUB>i</SUB> = 0.529 ± 0.022 mM). Kinetic measurements by real-time interval assay showed that pyrogallol induced rapid inactivation process composing with slight activations at the low dose. Spectrofluorimetry studies showed that pyrogallol mainly induced regional changes in the active site of tyrosinase accompanying with hydrophobic disruption at high dose. The computational MD simulations further revealed that pyrogallol could interact with several residues near the tyrosinase active site pocket such as HIS61, HIS85, HIS259, ASN260, HIS263, VAL283, and ALA296. Our study provides insight into the mechanism by which hydroxyl group composing pyrogallol inhibit tyrosinase and pyrogallol is a potential natural anti-pigmentation agent.</P>

Inhibitory effect of raspberry ketone on α-glucosidase: Docking simulation integrating inhibition kinetics

Xiong, Shang-Ling,Yue, Li-Mei,Lim, Gyu Tae,Yang, Jun-Mo,Lee, Jinhyuk,Park, Yong-Doo Elsevier 2018 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.113 No.-

<P><B>Abstract</B></P> <P>Inhibition of α-glucosidase is directly associated with treatment of type 2 diabetes. In this regard, we conducted enzyme kinetics integrated with computational docking simulation to assess the inhibitory effect of raspberry ketone (RK) on α-glucosidase. RK bound to the active site of α-glucosidase and interacted with several key residues such as ASP68, TYR71, HIS111, PHE157, PHE158, PHE177, GLN181, ASP214, THR215, ASP349, ASP408, and ARG439, as detected by protein-ligand docking simulation. Subsequently, we confirmed the action of RK on α-glucosidase as the non-competitive type of inhibition in a reversible and rapidly binding manner. The relevant kinetic parameters were <I>IC</I> <SUB>50</SUB> =6.17±0.46mM and <I>K</I> <SUB> <I>i</I> </SUB> =7.939±0.211mM. Regarding the structure-activity relationship, the higher concentration of RK induced slight modulation of the shape of the active site as monitored by hydrophobic exposure. The tertiary conformational change was linked to RK inhibition, and mostly involved regional changes of the active site. Our study provides insight into the functional role of RK due to its structural property of a hydroxyphenyl ring that interacts with the active site of α-glucosidase. We suggest that similar hydroxyphenyl ring compounds targeting the key residues of the active site might be potential α-glucosidase inhibitors.</P>

Sleep and Obesity

Chenzhao Ding,Lee Ling Lim,Li Xu,Alice Pik Shan Kong 대한비만학회 2018 The Korean journal of obesity Vol.27 No.1

Rising global prevalence and incidence of obesity lead to increased cardiovascular-renal complications and cancers. Epidemiological studies reported a worldwide trend towards suboptimal sleep duration and poor sleep quality in parallel with this obesity epidemic. From rodents and human models, it is highly plausible that abnormalities in sleep, both quantity and quality, impact negatively on energy metabolism. While excess dietary intake and physical inactivity are the known drivers of the obesity epidemic, promotion of healthy sleep habits has emerged as a new target to combat obesity. In this light, present review focuses on the existing literature examining the relationship between sleep physiology and energy homeostasis. Notably, sleep dysregulation perturbs the metabolic milieu via alterations in hormones such as leptin and ghrelin, eating behavior, neuroendocrine and autonomic nervous systems. In addition, shift work and trans-meridian air travel may exert a negative influence on the hypothalamic-pituitary-adrenal axis and trigger circadian misalignment, leading to impaired glucose tolerance and increased fat accumulation. Amassing evidence has also suggested that uncoupling of the circadian clock can increase the risk of adverse metabolic health. Given the importance of sleep in maintaining energy homeostasis and that it is potentially modifiable, promoting good sleep hygiene may create new avenues for obesity prevention and treatment.

Non-Hodgkin’s Lymphoma Presenting as Intracardiac Mass: A Rare Presentation

Caryn Tsujean Lim,Yik Hon Ho,Hwei Sung Ling,Bui Khiong Chung,Grace Wan Chieng Lee,Tze Shin Leong,Yen Yee Oon,Lee Ping Chew 아시아심장혈관영상의학회 2023 Cardiovascular Imaging Asia Vol.7 No.1

Primary cardiac lymphoma (PCL) comprises of 1%–2% of primary cardiac tumors. This case report describes a rare case of PCL with rapid disease progression. A 51-year-old female presented with 6 months of dyspnea. Her transthoracic echocardiogram showed a large exudative circumferential pericardial effusion and bi-atrial masses. An endovascular tissue biopsy using intra-cardiac echocardiography guidance enabled the diagnosis of diffuse large B-cell lymphoma. Staging computed tomography staged the disease at Ann Arbor stage IV E. She achieved a complete response to rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone chemoimmunotherapy.