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Impact of diabetes mellitus on osteoarthritis: a scoping review on biomarkers

Seow SR, Mat S, Ahmad Azam A, Rajab NF, Safinar Ismail I, Singh DKA, et al.

Expert Rev Mol Med, 2024 Apr 12;26:e8.
PMID: 38606593 DOI: 10.1017/erm.2024.7

Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs , ). Early management is important in order to avoid disability uphold quality of life (Ref. ). However, a lack of awareness of subclinical and early symptomatic stages of OA often hampers early management (Ref. ). Moreover, late diagnosis of OA among those with severe disease, at a stage when OA management becomes more complicated is common (Refs , , , ). Established risk factors for the development and progression of OA include increasing age, female, history of trauma and obesity (Ref. ). Recent studies have also drawn a link between OA and metabolic syndrome, which is characterized by insulin resistance, dyslipidaemia and hypertension (Refs , ).
Fulltext The role of Hibiscus sabdariffa L. (Roselle) in maintenance of ex vivo murine bone marrow-derived hematopoietic stem cells

Abdul Hamid Z, Lin Lin WH, Abdalla BJ, Bee Yuen O, Latif ES, Mohamed J, et al.

ScientificWorldJournal, 2014;2014:258192.
PMID: 25405216 DOI: 10.1155/2014/258192

Hematopoietic stem cells- (HSCs-) based therapy requires ex vivo expansion of HSCs prior to therapeutic use. However, ex vivo culture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role of Hibiscus sabdariffa L. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0-1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival (P < 0.05) of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1(+) cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased (P < 0.05) the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.
3,5-dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells

Roslie H, Chan KM, Rajab NF, Velu SS, Kadir SA, Bunyamin I, et al.

J Toxicol Sci, 2012 Feb;37(1):13-21.
PMID: 22293408

A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy- and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC(50)s of 78 µM, 38 µM, 67 µM and 19.5 µM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.
Seasonal variation and size distribution of inorganic and carbonaceous components, source identification of size-fractioned urban air particles in Kuala Lumpur, Malaysia

Jamhari AA, Latif MT, Wahab MIA, Hassan H, Othman M, Abd Hamid HH, et al.

Chemosphere, 2022 Jan;287(Pt 4):132309.
PMID: 34601373 DOI: 10.1016/j.chemosphere.2021.132309

This study aims to determine the inorganic and carbonaceous components depending on the seasonal variation and size distribution of urban air particles in Kuala Lumpur. Different fractions of particulate matter (PM) were measured using a Nanosampler from 17 February 2017 until 27 November 2017. The water-soluble inorganic ions (WSIIs) and carbonaceous components in all samples were analysed using ion chromatography and carbon analyser thermal/optical reflectance, respectively. Total PM concentration reached its peak during the southwest (SW) season (70.99 ± 6.04 μg/m3), and the greatest accumulation were observed at PM0.5-1.0 (22%-30%, 9.55 ± 1.03 μg/m3) and PM2.5-10 (22%-25%, 10.34 ± 0.81 μg/m3). SO42-, NO3- and NH4+ were major contributors of WSIIs, and their formation was favoured mainly during SW season (80.5% of total ions). PM0.5-1.0 and PM2.5-10 exhibited the highest percentage of WSII size distribution, accounted for 28.4% and 13.5% of the total mass, respectively. The average contribution of carbonaceous species (OC + EC) to total carbonaceous concentrations were higher in PM0.5-1.0 (35.2%) and PM2.5-10 (26.6%). Ultrafine particles (PM<0.1) consistently indicated that the sources were from vehicle emission while the SW season was constantly dominated by biomass burning sources. Using the positive matrix factorization (PMF) model, secondary inorganic aerosol and biomass burning (30.3%) was known as a significant source of overall PM. As a conclusion, ratio and source apportionment indicate the mixture of biomass burning, secondary inorganic aerosols and motor vehicle contributed to the size-segregated PM and seasonal variation of inorganic and carbonaceous components of urban air particles.
Fulltext Polygonumins A, a newly isolated compound from the stem of Polygonum minus Huds with potential medicinal activities

Ahmad R, Sahidin I, Taher M, Low C, Noor NM, Sillapachaiyaporn C, et al.

Sci Rep, 2018 03 09;8(1):4202.
PMID: 29523802 DOI: 10.1038/s41598-018-22485-5

Polygonumins A, a new compound, was isolated from the stem of Polygonum minus. Based on NMR results, the compound's structure is identical to that of vanicoside A, comprising four phenylpropanoid ester units and a sucrose unit. The structure differences were located at C-3″″'. The cytotoxic activity of polygonumins A was evaluated on several cancer cell lines by a cell viability assay using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The compound showed the highest antiproliferative (p
Fulltext Cytoprotection, Genoprotection, and Dermal Exposure Assessment of Chitosan-Based Agronanofungicides

Maluin FN, Hussein MZ, Yusof NA, Idris AS, Daim LDJ, Sarian MN, et al.

Pharmaceutics, 2020 May 29;12(6).
PMID: 32486034 DOI: 10.3390/pharmaceutics12060497

Health risks which result from exposure to pesticides have sparked awareness among researchers, triggering the idea of developing nanoencapsulation pesticides with the aim to enhance cytoprotection as well as genoprotection of the pesticides. In addition, nanocapsules of pesticides have slow release capability, high bioavailability, and site-specific delivery, which has attracted great interest from researchers. Hence, the objective of this work is to synthesize a nanoformulation of a fungicide of different sizes, namely, chitosan-hexaconazole nanoparticles (18 nm), chitosan-dazomet nanoparticles (7 nm), and chitosan-hexaconazole-dazomet nanoparticles (5 nm), which were then subjected to toxicological evaluations, including cytotoxicity, genotoxicity, cell death assay, and dermal irritation assays. Incubation of chitosan-based nanofungicides with V79-4 hamster lung cell did not reveal cytotoxicity or genotoxicity, potentially suggesting that encapsulation with chitosan reduces direct toxicity of the toxic fungicides. Meanwhile, pure fungicide revealed its high cytotoxic effect on V79-4 hamster lung cells. In addition, dermal exposure assessment on rabbits revealed that chitosan-hexaconazole nanoparticles are classified under corrosive subcategory 1C, while chitosan-dazomet nanoparticles are classified under corrosive subcategory 1B. Moreover, both chitosan-hexaconazole nanoparticles and chitosan-dazomet nanoparticles are classified as causing mild irritation.
Fulltext Neuroprotection of Tropical Fruit Juice Mixture via the Reduction of iNOS Expression and CRH Level in β-Amyloid-Induced Rats Model of Alzheimer's Disease

Ooi TC, Ahmad Munawar M, Mohd Rosli NH, Abdul Malek SNA, Rosli H, Ibrahim FW, et al.

Evid Based Complement Alternat Med, 2020;2020:5126457.
PMID: 32382294 DOI: 10.1155/2020/5126457

This study aimed to determine the effects of tropical fruit juice mixture (pomegranate, white guava, and Roselle) on biochemical, behavioral, and histopathological changes of β-amyloid- (Aβ-) induced rats. Formulation 8 (F8) of tropical fruit juice mixture was chosen for this present study due to its high phenolic content and antioxidant capacity. Forty Wistar male rats were divided into five groups: dPBS (sham-operated control), dAβ (Aβ control), JPBS (F8 and PBS), JAβ (F8 and Aβ), and IBFAβ (ibuprofen and Aβ). F8 (5 ml/kg BW), and ibuprofen (10 ml/kg BW) was given orally daily for four weeks before the intracerebroventricular infusion of Aβ for two weeks. Histological analysis and neuronal count of hippocampus tissue in the Cornu Ammonis (CA1) region showed that supplementation with F8 was able to prevent Aβ-induced tissue damage and neuronal shrinkage. However, no significant difference in locomotor activity and novel object recognition (NOR) percentage was detected among different groups at day 7 and day 14 following Aβ infusion. Only effect of time differences (main effect of day) was observed at day 7 as compared to day 14, where reduction in locomotor activity and NOR percentage was observed in all groups, with F (1, 7) = 6.940, p < 0.05 and F (1, 7) = 7.152, p < 0.05, respectively. Besides, the MDA level of the JAβ group was significantly lower (p < 0.01) than that of the dPBS group. However, no significant changes in SOD activity were detected among different groups. Significant reduction in plasma CRH level (p < 0.05) and iNOS expression (p < 0.01) in the brain was detected in the JAβ group as compared to the dAβ group. Hence, our current findings suggest that the tropical fruit juice mixture (F8) has the potential to protect the rats from Aβ-induced neurotoxicity in brain hippocampus tissue possibly via its antioxidant properties and the suppression of iNOS expression and CRH production.
Fulltext Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults

Shahar S, Omar A, Vanoh D, Hamid TA, Mukari SZ, Din NC, et al.

Aging Clin Exp Res, 2016 Dec;28(6):1089-1104.
PMID: 26670602 DOI: 10.1007/s40520-015-0511-4

A number of longitudinal studies on aging have been designed to determine the predictors of healthy longevity, including the neuroprotective factors, however, relatively few studies included a wide range of factors and highlighted the challenges faced during data collection. Thus, the longitudinal study on neuroprotective model for healthy longevity (LRGS TUA) has been designed to prospectively investigate the magnitude of cognitive decline and its risk factors through a comprehensive multidimensional assessment comprising of biophysical health, auditory and visual function, nutrition and dietary pattern and psychosocial aspects. At baseline, subjects were interviewed for their status on sociodemographic, health, neuropsychological test, psychosocial and dietary intake. Subjects were also measured for anthropometric and physical function and fitness. Biospecimens including blood, buccal swap, hair and toenail were collected, processed and stored. A subsample was assessed for sensory function, i.e., vision and auditory. During follow-up, at 18 and 36 months, most of the measurements, along with morbidity and mortality outcomes will be collected. The description of mild cognitive impairment, successful aging and usual aging process is presented here. A total 2322 respondents were recruited in the data analysis at baseline. Most of the respondents were categorized as experiencing usual aging (73 %), followed by successful aging (11 %) and mild cognitive impairment (16 %). The LRGS TUA study is the most comprehensive longitudinal study on aging in Malaysia, and will contribute to the understanding of the aging process and factors associated with healthy aging and mental well-being of a multiethnic population in Malaysia.
Methodology approaches and challenges in population-based longitudinal study of a neuroprotective model for healthy longevity

Lau H, Shahar S, Hussin N, Kamarudin MZ, Hamid TA, Mukari SZ, et al.

Geriatr Gerontol Int, 2019 Mar;19(3):233-239.
PMID: 30618211 DOI: 10.1111/ggi.13598

AIM: The 36-month Long-Term Research Grant Scheme project: Towards Usual Aging - Neuroprotective Model for Healthy Longevity among Malaysian Elderly was designed to address multidimensional aspects including psychosocial, biophysical health, nutrition and dietary pattern, and auditory and visual function to highlight the magnitude of these associations in a single study.
METHODS: A total of 2322 respondents aged ≥60 years were recruited at baseline using the multistage sampling method, followed up at 18 months and 36 months.
RESULTS: Response rates at baseline, 18 months and 36 months were 87.8%, 77.3% and 67.1%, respectively. At baseline, the prevalence of successful aging, usual aging and mild cognitive impairment was 11%, 73% and 16%, respectively. The prevalence of single and multimorbidity at baseline were 25.9% and 50.3%, respectively. The incidence rates of mild cognitive impairment at 18 months and 36 months were 6.5 and 5.6 per 100 person-years. The incidence rates of multimorbidity at 18 months and 36 months were 23.7 and 21.5 per 100 person-years, respectively.
CONCLUSIONS: The Long-Term Research Grant Scheme project: Towards Usual Aging study provides an opportunity to investigate the interactions between wide ranges of aspects of the older population in a nationally representative sample of the older population. Geriatr Gerontol Int 2019; 19: 233-239.
Fulltext The association of nuclear abnormalities in exfoliated buccal epithelial cells with the health status of different agricultural activities farmers in Peninsular Malaysia

Abdul Hamid Z, Mohd Zulkifly MF, Hamid A, Lubis SH, Mohammad N, Ishak I, et al.

Genes Environ, 2016;38:7.
PMID: 27350827 DOI: 10.1186/s41021-016-0032-1

Pesticide exposure possesses risk of genotoxicity to humans, particularly farmers. Despite accumulating evidences linking genotoxicity to pesticide exposure, epidemiological studies to address pesticide toxicity in occupationally exposed farmers in Malaysia remain underreported. Thus, this study was aimed to determine the presence of nuclear abnormalities through the assessment of micronucleus (MN) and binucleus (BNu) frequencies in exfoliated buccal epithelial cells from farmers who were exposed to pesticides. A cross-sectional study of farmers among different agricultural activities farmers in Bachok and Pasir Puteh, Kelantan, North East of Peninsular Malaysia was done to evaluate the presence of nuclear abnormalities and its correlation with their health status and farming activities.
Fulltext Multidomain Intervention for Reversal of Cognitive Frailty, Towards a Personalized Approach (AGELESS Trial): Study Design

Ponvel P, Shahar S, Singh DKA, Ludin AFM, Rajikan R, Rajab NF, et al.

J Alzheimers Dis, 2021;82(2):673-687.
PMID: 34092633 DOI: 10.3233/JAD-201607

BACKGROUND: Cognitive frailty (CF) is identified as one of the main precursors of dementia. Multidomain intervention has been found to delay or prevent the onset of CF.
OBJECTIVE: The aim of our present study is to determine the effectiveness of a comprehensive, multidomain intervention on CF; to evaluate its cost effectiveness and the factors influencing adherence toward this intensive intervention.
METHODS: A total of 1,000 community dwelling older adults, aged 60 years and above will be screened for CF. This randomized controlled trial involves recruitment of 330 older adults with CF from urban, semi-urban, and rural areas in Malaysia. Multidomain intervention comprised of physical, nutritional, cognitive, and psychosocial aspects will be provided to participants in the experimental group (n = 165). The control group (n = 165) will continue their usual care with their physician. Primary outcomes include CF status, physical function, psychosocial and nutritional status as well as cognitive performance. Vascular health and gut microbiome will be assessed using blood and stool samples. A 24-month intensive intervention will be prescribed to the participants and its sustainability will be assessed for the following 12 months. The effective intervention strategies will be integrated as a personalized telerehabilitation package for the reversal of CF for future use.
RESULTS: The multidomain intervention developed from this trial is expected to be cost effective compared to usual care as well as able is to reverse CF.
CONCLUSION: This project will be part of the World-Wide FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) Network, of which common identifiable data will be shared and harmonized among the consortia.

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