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Fulltext Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities

Ramasamy TS, Yee YM, Khan IM

Front Cell Dev Biol, 2021;9:625497.
PMID: 34336816 DOI: 10.3389/fcell.2021.625497

Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.
Survival and immunomodulation of stem cells from human extracted deciduous teeth expanded in pooled human and foetal bovine sera

Haque N, Khan IM, Abu Kasim NH

Cytokine, 2019 08;120:144-154.
PMID: 31071675 DOI: 10.1016/j.cyto.2019.04.018

The immunomodulatory properties of mesenchymal stem cells (MSCs) from autologous and allogeneic sources are useful in stimulating tissue regeneration and repair. To obtain a high number of MSCs for transplantation requires extensive in vitro expansion with culture media supplements that can cause xeno-contamination of cells potentially compromising function and clinical outcomes. In this study stem cells from human extracted deciduous teeth (SHED) were cultured in Knockout™ DMEM supplemented with either pooled human serum (pHS) or foetal bovine serum (FBS) to compare their suitability in maintaining immunomodulatory properties of cells during in vitro expansion. No significant difference in cell survival of SHED grown in pHS (pHS-SHED) or FBS (FBS-SHED) was observed when co-cultured with complement, monocytes or lymphocytes. However, significant changes in the expression of sixteen paracrine factors involved in immunomodulation were observed in the supernatants of FBS-SHED co-cultures with monocytes or lymphocytes compared to that in pHS-SHEDs after both 24 and 120 h of incubation. Further analysis of changing protein levels of paracrine factors in co-cultures using biological pathway analysis software predicted upregulation of functions associated with immunogenicity in FBS-SHED and lymphocyte co-cultures compared to pHS-SHED co-cultures. Pathway analysis also predicted significant stimulation of HMGB1 and TREM1 signalling pathways in FBS-SHED co-cultures indicating activation of immune cells and inflammation. Though FBS supplementation does not impact survival of SHED, our combinatorial biological pathway analysis supports the idea that in vitro expansion of SHEDs in pHS provides optimal conditions to minimise xeno-contamination and inflammation and maintain their immunomodulatory properties.
Three-dimensional image analysis of developing mandibular third molars apices for age estimation: A study using CBCT data enhanced with Mimics & 3-Matics software

Asif MK, Nambiar P, Ibrahim N, Al-Amery SM, Khan IM

Leg Med (Tokyo), 2019 Jul;39:9-14.
PMID: 31158731 DOI: 10.1016/j.legalmed.2019.05.003

Three-dimensional imaging has improved the method of analysis in many forensic science investigations. The study aimed to derive regression equation for age estimation by investigating the relationship between chronological age and surface area of the developing mandibular 3rd molars apices. Furthermore, other predictor variables: ethnicity (Malay and Chinese), gender and status of the root development completion (open/closed apices) were also investigated in terms of fit to the age estimation model. One hundred and twenty eight training and 55 validation samples of intact mandibular 3rd molars were selected from 183 CBCT scans. The samples comprised of 93 Malays and 90 Chinese, ranging in age from 13 to 24 years. Three-dimensional image modeling and surface area analysis of the developing mandibular 3rd molars apices were performed using Mimics and 3-Matics software. Multiple linear regression analysis was used to derive age estimation model using chronological age as a dependent variable and surface area of the apices, ethnicity, gender and status of the root development completion (open/closed apices) as predictor variables. A strong inverse correlation (r = 0.95, SD = 1.144) was observed between chronological age and all the predictor variables. The results showed that 89.6% of the variation in age can be explained by the predictor variables. Mean absolute error (MAE) value of 0.8223 was observed when the derived regression equation was tested on the independent validation sample. In conclusion, three-dimensional surface area analysis of the developing mandibular 3rd molars apices can be used as a reliable method for age estimation.
Fulltext Pre-schoolers' tooth brushing behaviour and association with their oral health: a cross sectional study

Khan IM, Mani SA, Doss JG, Danaee M, Kong LYL

BMC Oral Health, 2021 Jun 02;21(1):283.
PMID: 34078349 DOI: 10.1186/s12903-021-01643-8

BACKGROUND: Toothbrushing is an important yet neglected behaviour that affects the oral health of preschool children. Little is reported on parental supervision, an essential aspect of routine effective toothbrushing in this age group. The aim of this study was to evaluate pre-schoolers' toothbrushing behaviour including parental involvement and its association with their oral health.
METHODS: This was a cross-sectional study. A total of 92 preschool children (4-6 years) were invited to participate with their parents/guardians. Nine parameters of toothbrushing behaviour were assessed from parental responses (questionnaire) and observation of child and parents/guardians (video recording). Oral examination included recording plaque, gingival and dental caries indices. BORIS software was used to assess toothbrushing parameters and Smart PLS was used to perform association with a second-generation multivariate analysis to create models with and without confounding factors.
RESULTS: Girls were slightly more (53%) than boys (47%). Children aged 4 years were slightly more in number (38%), followed by 6-year-olds and 5-year-olds. Nearly, 90% parents had tertiary education and 46% had more than 2 children. Differences were recorded in the reported and observed behaviour. Thirty-five percent parents/guardians reported using pea-size toothpaste amount but only 28% were observed. Forty percent reported to brush for 30 s-1 min, however 51% were observed to brush for 1-2 min. Half the children were observed to use fluoridated toothpaste (F
Dental age estimation in Malaysian adults based on volumetric analysis of pulp/tooth ratio using CBCT data

Asif MK, Nambiar P, Mani SA, Ibrahim NB, Khan IM, Lokman NB

Leg Med (Tokyo), 2019 Feb;36:50-58.
PMID: 30415192 DOI: 10.1016/j.legalmed.2018.10.005

Forensic odontology plays an important role in human identification and dental age estimation is an integral part of this process. The aim of the study was to investigate the association between chronological age and pulp/tooth volume ratio in a Malaysian population (Malays and Chinese) from cone-beam computed tomography (CBCT) scans, enhanced with Mimics software. Three hundred CBCT scans of 153 males and 147 females, aged between 16 and 65 years were divided into 5 age groups. Volumetric analysis of the pulp/tooth ratio was performed in maxillary left canines, maxillary right canines and maxillary right central incisors. Simple linear regression and Pearson correlation analysis indicated the strongest coefficient of correlation (R) values for maxillary right central incisors (0.83) followed by maxillary right canines (0.74) and maxillary left canines (0.73). Fisher's Z test indicated that dental age estimation is gender independent. The derived regression equations were further validated on an independent group of 126 teeth. The results indicated mean absolute error (MAE) values of 6.48 and 8.58 years for maxillary right central incisors and maxillary canines respectively. It was also noticed that MAE values were higher among the age groups ranging from 46 to 65 years. This study showed that a volumetric change in the pulp cavity with age is a valuable assessment method for dental age estimation among Malaysian population.
Dental age estimation employing CBCT scans enhanced with Mimics software: Comparison of two different approaches using pulp/tooth volumetric analysis

Asif MK, Nambiar P, Mani SA, Ibrahim NB, Khan IM, Sukumaran P

J Forensic Leg Med, 2018 Feb;54:53-61.
PMID: 29324319 DOI: 10.1016/j.jflm.2017.12.010

The methods of dental age estimation and identification of unknown deceased individuals are evolving with the introduction of advanced innovative imaging technologies in forensic investigations. However, assessing small structures like root canal volumes can be challenging in spite of using highly advanced technology. The aim of the study was to investigate which amongst the two methods of volumetric analysis of maxillary central incisors displayed higher strength of correlation between chronological age and pulp/tooth volume ratio for Malaysian adults. Volumetric analysis of pulp cavity/tooth ratio was employed in Method 1 and pulp chamber/crown ratio (up to cemento-enamel junction) was analysed in Method 2. The images were acquired employing CBCT scans and enhanced by manipulating them with the Mimics software. These scans belonged to 56 males and 54 females and their ages ranged from 16 to 65 years. Pearson correlation and regression analysis indicated that both methods used for volumetric measurements had strong correlation between chronological age and pulp/tooth volume ratio. However, Method 2 gave higher coefficient of determination value (R2 = 0.78) when compared to Method 1 (R2 = 0.64). Moreover, manipulation in Method 2 was less time consuming and revealed higher inter-examiner reliability (0.982) as no manual intervention during 'multiple slice editing phase' of the software was required. In conclusion, this study showed that volumetric analysis of pulp cavity/tooth ratio is a valuable gender independent technique and the Method 2 regression equation should be recommended for dental age estimation.
Enhancing the three-dimensional visualization of a foreign object using Mimics software

Asif MK, Nambiar P, Khan IM, Aziz ZABCA, Noor NSBM, Shanmuhasuntharam P, et al.

Radiol Case Rep, 2019 Dec;14(12):1545-1549.
PMID: 31719943 DOI: 10.1016/j.radcr.2019.10.001

A patient was referred to the Oral and Maxillofacial Imaging Division and the attending dental specialist suspected a foreign object at the anterior region of the maxilla. The region was scanned using Kodak 9000 3D cone-beam computed tomography (CBCT) extraoral imaging system (Carestream Health, Inc.) to determine the type and morphometric characteristic of foreign object. The CBCT images failed to determine the identity and nature of the foreign object. CBCT images were then exported to the Materialise Interactive Medical Image Control System (Mimics) software to evaluate whether this software can help in enhancing the visualization of the foreign object in the maxillofacial region. The findings showed that there was an improved visualization of the foreign body and the type of the object could be determined with certainty. The object was identified as an endodontic file and was clearly visible when visualized as a reconstructed 3D model in Mimics software. Although the identification of abnormalities has been dramatically improved using 3D scans, the visualization can be further enhanced using image processing software like Mimics.