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Cell-Penetrating Peptides: Correlation between Peptide-Lipid Interaction and Penetration Efficiency

Her Choong F, Keat Yap B

Chemphyschem, 2021 03 03;22(5):493-498.
PMID: 33377300 DOI: 10.1002/cphc.202000873

Cell-penetrating peptides are used in the delivery of peptides and biologics, with some cell-penetrating peptides found to be more efficient than others. The exact mechanism of how they interact with the cell membrane and penetrate it, however, remains unclear. This study attempts to investigate the difference in free energy profiles of three cell-penetrating peptides (TAT, CPP1 and CPP9) with a model lipid bilayer (DOPC) using molecular dynamics pulling simulations with umbrella sampling. Potential mean force (PMF) and free energy barrier between the peptides and DOPC are determined using WHAM analysis and MM-PBSA analysis, respectively. CPP9 is found to have the smallest PMF value, followed by CPP1 and TAT, consistent with the experimental data. YDEGE peptide, however, does not give the highest PMF value, although it is a non-cell-permeable peptide. YDEGE is also found to form water pores, alongside with TAT and CPP9, suggesting that it is difficult to distinguish true water pore formation from artefacts arising from pulling simulations. On the contrary, free energy analysis of the peptide-DOPC complex at the lipid-water interface with MM-PBSA provides results consistent with experimental data with CPP9 having the least interaction with DOPC and lowest free energy barrier, followed by CPP1, TAT and YDEGE. These findings suggest that peptide-lipid interaction at the lipid-water interface has a direct correlation with the penetration efficiency of peptides across the lipid bilayer.
Dengue fever complicated by pulmonary haemorrhage manifesting as haemoptysis

Liam CK, Yap BH, Lam SK

J Trop Med Hyg, 1993 Jun;96(3):197-200.
PMID: 8505777

A 17-year-old girl was admitted to hospital with dengue fever. On the ninth day of fever she developed haemoptysis and chest X-ray changes consistent with haemorrhage in her lungs. Thrombocytopaenia and mild coagulopathy were the most likely cause of this unusual haemoptysis in this patient. Investigations excluded other causes for the haemoptysis.
Melioidosis pneumonia and blast injury

Wang CY, Yap BH, Delilkan AE

Chest, 1993 Jun;103(6):1897-9.
PMID: 8404124

We present the case of a 24-year-old woman with acute septicemic melioidosis resulting from inhaled infective dust during a blast injury. With appropriate antibiotic treatment and supportive therapy in the ICU, the patient made an uneventful recovery.
Fulltext Use of pressurised aerosol inhalers among patients attending the Chest Clinic and Primary Care Department of University Hospital, Kuala Lumpur

Liam CK, Lo YL, Yap BH, Low SH, Ariwalagam M

Med J Malaysia, 1993 Sep;48(3):273-9.
PMID: 8183138

Eighty consecutive patients who came to collect their prescriptions for pressurised aerosol inhalers at the Pharmacy of the University Hospital, Kuala Lumpur, were interviewed regarding their use of the pressurised inhaler. Their inhaler technique was also assessed. A significant proportion inhaled the steroid aerosol before the bronchodilator and 23.5% used the steroid inhaler for relief of acute dyspnoea. Only 28.8% of the 80 patients performed correctly all 6 steps necessary for the proper use of inhalers. The most common mistake was the failure to inhale slowly and deeply. Patients who had used the device for more than 5 years performed better, while correct inhaler technique was not dependent on the patient's sex, age or level of education.

Study site: Chest clinic, University Malaya Medical Centre (UMMC)
Roles of Ki67 in Breast Cancer - Important for Management?

Yip Ch, Bhoo-Pathy N, Daniel J, Foo Y, Mohamed A, Abdullah M, et al.

Asian Pac J Cancer Prev, 2016;17(3):1077-82.
PMID: 27039727

BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer.
MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22.
RESULTS: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy.
CONCLUSIONS: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.
Porphyrin Acceptors with Two Perylene Diimide Dimers for Organic Solar Cells

Pan X, Wu J, Xiao L, Yap B, Xia R, Peng X

ChemSusChem, 2021 Sep 06;14(17):3614-3621.
PMID: 34107177 DOI: 10.1002/cssc.202100787

Three small-molecule acceptors (Por-PDI, TEHPor-PDI, and BBOPor-PDI) with different side chains were synthesized by using a porphyrin core as the electron-donating unit and connecting electron-withdrawing perylene diimide dimers via acetylene bridges. The bulk heterojunction organic solar cells based on the three acceptors and a polymer donor provided power conversion efficiencies (PCEs) of 3.68-5.21 % when the active layers were fabricated with pyridine additives. Though the synthesis of Por-PDI is easier with fewer reaction steps and higher yields, the devices based on Por-PDI showed the best performance with a PCE of 5.21 %. The more ordered intermolecular packing due to the reduced steric hindrance at the porphyrin core of Por-PDI could contribute to the more balanced hole/electron mobilities, higher maximum charge generation rate, and less bimolecular recombination in Por-PDI devices, which are beneficial for the higher PCE.
High-quality WS2 film as a hole transport layer in high-efficiency non-fullerene organic solar cells

Wang X, Liu P, Yap B, Xia R, Wong WY, He Z

Nanoscale, 2021 Oct 14;13(39):16589-16597.
PMID: 34585178 DOI: 10.1039/d1nr03728e

Liquid-exfoliated 2D transition metal disulfides (TMDs) are potential substitutes for poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as hole transport layers (HTLs) in Organic Solar Cells (OSCs). Herein, high-yield and high-quality WS2 flake layers are prepared by comprehensively controlling the initial concentration, sonication processing time and centrifugal speed. The WS2 layers deposited on in situ transparent indium tin oxide (ITO) without plasma treatment show higher uniformity and conductivity than that formed on ITO after plasma treatment. With a significant increase in the short-circuit current density (JSC), the power conversion efficiency (PCE) of PM6:Y6-based non-fullerene OSCs using optimized WS2 as the HTL is higher than that using PEDOT:PSS as the HTL(15.75% vs. 15.31%). Combining the morphology characteristics with carrier recombination characteristics, the higher quality of the ITO/WS2 composite substrate leads to better charge transport and a lower bimolecular recombination rate in OSCs, thereby improving the device performance.
Perceptions, attitudes and beliefs towards soya among healthy Asian women participating in a soya randomised controlled trial

Yap B, Rajaram N, Ho WK, Khor GL, Teo SH

J Nutr Sci, 2023;12:e69.
PMID: 37457681 DOI: 10.1017/jns.2023.48

The soya-breast cancer risk relationship remains controversial in Asia due to limited and inconsistent research findings and is exacerbated by difficulties in recruiting and retaining participants in intervention trials. Understanding public perceptions towards soya is important for designing effective intervention trials. Here, we administered a close-ended, quantitative survey to healthy, peri- and post-menopausal Asian women in the Malaysian Soy and Mammographic Density (MiSo) Study to assess perception towards soya and explore motivators and barriers that affect study adherence using the Capability, Opportunity, Motivation and Belief (COM-B) Model and Theoretical Domains Framework (TDF). Of 118 participants, the majority reported the belief that soya promotes good health (Supplement = 85⋅7 %, Diet = 90⋅0 %, Control = 87⋅9 %). Most participants reported obtaining information about soya from the internet (Supplement = 61⋅0 %, Diet = 55⋅3 %, Control = 35⋅9 %), while health professionals were least reported (Supplement = 9⋅8 %, Diet = 7⋅9 %, Control = 5⋅1 %). Stratified analyses by study completion and adherence status yielded comparable findings. By the end of the study, dietary arm participants reported a strong belief that soya has no impact on their health (Supplement = 7⋅1 % v. Diet = 20⋅0 % v. Control = 0⋅0 %, P = 0⋅012). Motivation and opportunity strongly facilitated soya consumption, while psychological capability was the most common barrier to consumption though less evident among dietary arm participants. While most Asian women have a positive perception towards soya, theory-based intervention trials are warranted to understand the perception-study adherence relationship and to accurately inform the public of the health effects of soya.