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Fulltext miRNAS as potential biomarkers in head and neck squamous cell carcinoma diagnostics

Cheah Yoke Kqueen, Yaghma Masood, Nurul Syakima Ab Mutalib, Sethu Thakachy Subha, Norhafizah Mohtarrudin

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):9-9.
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MicroRNAs (miRNAs) are small noncoding RNAs that involved in various normal and cancer-related cellular pro-cesses. Studies on expression profiling of miRNAs have been performed and the data showed that some miRNAs are up-regulated or down-regulated in cancer. miRNAs play a crucial role in HNSCC development, metastasis, prognosis and survival rate. Several studies have been conducted previously to investigate that use of miRNAs as the biomark-ers in disease diagnostic/prognostic and potential therapeutic targets management that may improve the outcomes of HNSCC. Our previous study revealed that upregulation of oncogenic miRNAs including hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a, hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221* were able to distinguish HNSCC from normal samples. These miRNAs may contribute in a simple profiling strategy to identify individuals at higher risk of developing head and neck cancers, thus helping in the elucidation of the molecular mechanisms involved in head and neck cancer pathogenesis.
Fulltext Anti-Metastatic and Anti-Angiogenic Effects of Curcumin Analog DK1 on Human Osteosarcoma Cells In Vitro

Aziz MNM, Rahim NFC, Hussin Y, Yeap SK, Masarudin MJ, Mohamad NE, et al.

Pharmaceuticals (Basel), 2021 Jun 03;14(6).
PMID: 34204873 DOI: 10.3390/ph14060532

Osteosarcoma (OS) is a life-threatening malignant bone tumor associated with poor prognosis among children. The survival rate of the patient is still arguably low even with intensive treatment provided, plus with the inherent side effects from the chemotherapy, which gives more unfavorable outcomes. Hence, the search for potent anti-osteosarcoma agent with promising safety profile is still on going. Natural occurring substance like curcumin has gained a lot of attention due to its splendid safety profile as well as it pharmacological advantages such as anti-metastasis and anti-angiogenesis. However, natural curcumin was widely known for its poor cellular uptake, which undermines all potential that it possesses. This prompted the development of synthetically synthesized curcuminoid analog, known as (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2- en-1-one (DK1). In this present study, in vitro scratch assay, transwell migration/invasion assay, HUVEC tube formation assay, and ex vivo rat aortic ring assays were performed in order to investigate the anti-metastatic and anti-angiogenic potential of DK1. For further comprehension of DK1 mechanism on human osteosarcoma cell lines, microarray gene expression analysis, quantitative polymerase chain reaction (qPCR), and proteome profiler were adopted, providing valuable forecast from the expression of important genes and proteins related to metastasis and angiogenesis. Based on the data gathered from the bioassays, DK1 was able to inhibit the metastasis and angiogenesis of human osteosarcoma cell lines by significantly reducing the cell motility, number of migrated and invaded cells as well as the tube formation and micro-vessels sprouting. Additionally, DK1 also has significantly regulated several cancer pathways involved in OS proliferation, metastasis, and angiogenesis such as PI3K/Akt and NF-κB in both U-2 OS and MG-63. Regulation of PI3K/Akt caused up-regulation of genes related to metastasis inhibition, namely, PTEN, FOXO, PLK3, and GADD45A. Meanwhile, NF-κB pathway was regulated by mitigating the expression of NF-κB activator such as IKBKB and IKBKE in MG-63, whilst up-regulating the expression of NF-κB inhibitors such as NFKBIA and NFKBIE in U-2 OS. Finally, DK1 also has successfully hindered the metastatic and angiogenic capability of OS cell lines by down-regulating the expression of pro-metastatic genes and proteins like MMP3, COL11A1, FGF1, Endoglin, uPA, and IGFBP2 in U-2 OS. Whilst for MG-63, the significantly down-regulated oncogenes were Serpin E1, AKT2, VEGF, uPA, PD-ECGF, and Endoglin. These results suggest that curcumin analog DK1 may serve as a potential new anti-osteosarcoma agent due to its anti-metastatic and anti-angiogenic attributes.
Fulltext Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

Aziz MNM, Hussin Y, Che Rahim NF, Nordin N, Mohamad NE, Yeap SK, et al.

Molecules, 2018 Jan 05;23(1).
PMID: 29303982 DOI: 10.3390/molecules23010075

Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of the natural substances that have been extensively studied due to its anti-cancer properties and is pharmacologically safe considering its ubiquitous consumption for centuries. However, curcumin suffers from a poor circulating bioavailability, which has led to the development of a chemically synthesized curcuminoid analog, namely (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1). In this study, the cytotoxic effects of the curcumin analog DK1 was investigated in both U-2OS and MG-63 osteosarcoma cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death was microscopically examined via acridine orange/propidium iodide (AO/PI) double staining. Flow cytometer analysis including Annexin V/Fluorescein isothiocyanate (FITC), cell cycle analysis and JC-1 were adapted to determine the mode of cell death. Subsequently in order to determine the mechanism of cell death, quantitative polymerase chain reaction (qPCR) and proteome profiling was carried out to measure the expression of several apoptotic-related genes and proteins. Results indicated that DK1 induced U-2 OS and MG-63 morphological changes and substantially reduced cell numbers through induction of apoptosis. Several apoptotic genes and proteins were steadily expressed after treatment with DK1; including caspase 3, caspase 9, and BAX, which indicated that apoptosis occurred through a mitochondria-dependent signaling pathway. In conclusion, DK1 could be considered as a potential candidate for an anti-osteosarcoma drug in the near future, contingent upon its ability to induce apoptosis in osteosarcoma cell lines.
Effect of organic-phase solvents on physicochemical properties and cellular uptake of astaxanthin nanodispersions

Anarjan N, Tan CP, Ling TC, Lye KL, Malmiri HJ, Nehdi IA, et al.

J Agric Food Chem, 2011 Aug 24;59(16):8733-41.
PMID: 21726079 DOI: 10.1021/jf201314u

A simplex centroid mixture design was used to study the interactions between two chosen solvents, dichloromethane (DCM) and acetone (ACT), as organic-phase components in the formation and physicochemical characterization and cellular uptake of astaxanthin nanodispersions produced using precipitation and condensation processes. Full cubic or quadratic regression models with acceptable determination coefficients were obtained for all of the studied responses. Multiple-response optimization predicted that the organic phase with 38% (w/w) DCM and 62% (w/w) ACT yielded astaxanthin nanodispersions with the minimum particle size (106 nm), polydispersity index (0.191), and total astaxanthin loss (12.7%, w/w) and the maximum cellular uptake (2981 fmol/cell). Astaxanthin cellular uptake from the produced nanodispersions also showed a good correlation with their particle size distributions and astaxanthin trans/cis isomerization ratios. The absence of significant (p > 0.05) differences between the experimental and predicted values of the response variables confirmed the adequacy of the fitted models.
Fulltext Landmark-based homologous multi-point warping approach to 3D facial recognition using multiple datasets

Agbolade O, Nazri A, Yaakob R, Ghani AAA, Cheah YK

PeerJ Comput Sci, 2020;6:e249.
PMID: 33816901 DOI: 10.7717/peerj-cs.249

Over the years, neuroscientists and psychophysicists have been asking whether data acquisition for facial analysis should be performed holistically or with local feature analysis. This has led to various advanced methods of face recognition being proposed, and especially techniques using facial landmarks. The current facial landmark methods in 3D involve a mathematically complex and time-consuming workflow involving semi-landmark sliding tasks. This paper proposes a homologous multi-point warping for 3D facial landmarking, which is verified experimentally on each of the target objects in a given dataset using 500 landmarks (16 anatomical fixed points and 484 sliding semi-landmarks). This is achieved by building a template mesh as a reference object and applying this template to each of the targets in three datasets using an artificial deformation approach. The semi-landmarks are subjected to sliding along tangents to the curves or surfaces until the bending energy between a template and a target form is minimal. The results indicate that our method can be used to investigate shape variation for multiple datasets when implemented on three databases (Stirling, FRGC and Bosphorus).
Fulltext 3-Dimensional facial expression recognition in human using multi-points warping

Agbolade O, Nazri A, Yaakob R, Ghani AA, Cheah YK

BMC Bioinformatics, 2019 Dec 02;20(1):619.
PMID: 31791234 DOI: 10.1186/s12859-019-3153-2

BACKGROUND: Expression in H-sapiens plays a remarkable role when it comes to social communication. The identification of this expression by human beings is relatively easy and accurate. However, achieving the same result in 3D by machine remains a challenge in computer vision. This is due to the current challenges facing facial data acquisition in 3D; such as lack of homology and complex mathematical analysis for facial point digitization. This study proposes facial expression recognition in human with the application of Multi-points Warping for 3D facial landmark by building a template mesh as a reference object. This template mesh is thereby applied to each of the target mesh on Stirling/ESRC and Bosphorus datasets. The semi-landmarks are allowed to slide along tangents to the curves and surfaces until the bending energy between a template and a target form is minimal and localization error is assessed using Procrustes ANOVA. By using Principal Component Analysis (PCA) for feature selection, classification is done using Linear Discriminant Analysis (LDA).
RESULT: The localization error is validated on the two datasets with superior performance over the state-of-the-art methods and variation in the expression is visualized using Principal Components (PCs). The deformations show various expression regions in the faces. The results indicate that Sad expression has the lowest recognition accuracy on both datasets. The classifier achieved a recognition accuracy of 99.58 and 99.32% on Stirling/ESRC and Bosphorus, respectively.
CONCLUSION: The results demonstrate that the method is robust and in agreement with the state-of-the-art results.
Fulltext Morphometric approach to 3D soft-tissue craniofacial analysis and classification of ethnicity, sex, and age

Agbolade O, Nazri A, Yaakob R, Ghani AA, Cheah YK

PLoS One, 2020;15(4):e0228402.
PMID: 32271782 DOI: 10.1371/journal.pone.0228402

BACKGROUND: The application of three-dimensional scan models offers a useful resource for studying craniofacial variation. The complex mathematical analysis for facial point acquisition in three-dimensional models has made many craniofacial assessments laborious.
METHOD: This study investigates three-dimensional (3D) soft-tissue craniofacial variation, with relation to ethnicity, sex and age variables in British and Irish white Europeans. This utilizes a geometric morphometric approach on a subsampled dataset comprising 292 scans, taken from a Liverpool-York Head Model database. Shape variation and analysis of each variable are tested using 20 anchor anatomical landmarks and 480 sliding semi-landmarks.
RESULTS: Significant ethnicity, sex, and age differences are observed for measurement covering major aspects of the craniofacial shape. The ethnicity shows subtle significant differences compared to sex and age; even though it presents the lowest classification accuracy. The magnitude of dimorphism in sex is revealed in the facial, nasal and crania measurement. Significant shape differences are also seen at each age group, with some distinct dimorphic features present in the age groups.
CONCLUSIONS: The patterns of shape variation show that white British individuals have a more rounded head shape, whereas white Irish individuals have a narrower head shape. White British persons also demonstrate higher classification accuracy. Regarding sex patterns, males are relatively larger than females, especially in the mouth and nasal regions. Females presented with higher classification accuracy than males. The differences in the chin, mouth, nose, crania, and forehead emerge from different growth rates between the groups. Classification accuracy is best for children and senior adult age groups.
Fulltext Investigation of age-related facial variation among Angelman syndrome patients

Agbolade O, Nazri A, Yaakob R, Ghani AA, Cheah YK

Sci Rep, 2021 10 21;11(1):20767.
PMID: 34675349 DOI: 10.1038/s41598-021-99944-z

Angelman syndrome (AS) is one of the common genetic disorders that could emerge either from a 15q11-q13 deletion or paternal uniparental disomy (UPD) or imprinting or UBE3A mutations. AS comes with various behavioral and phenotypic variability, but the acquisition of subjects for experiment and automating the landmarking process to characterize facial morphology for Angelman syndrome variation investigation are common challenges. By automatically detecting and annotating subject faces, we collected 83 landmarks and 10 anthropometric linear distances were measured from 17 selected anatomical landmarks to account for shape variability. Statistical analyses were performed on the extracted data to investigate facial variation in each age group. There is a correspondence in the results achieved by relative warp (RW) of the principal component (PC) and the thin-plate spline (TPS) interpolation. The group is highly discriminated and the pattern of shape variability is higher in children than other groups when judged by the anthropometric measurement and principal component.