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

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 , ).

The potential roles of lncRNA TINCR in triple negative breast cancer.

Triple negative breast cancer (TNBC) is the most aggressive intrinsic breast cancer subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and low levels of human epidermal growth factor receptor 2 (HER2). The complex nature of TNBC has resulted in little therapeutic progress for the past several decades. The standard of care remains the FEC cocktail (5-fluorouracil (5-FU), epirubicin and cyclophosphamide). However, early relapse and metastasis in TNBC patients persists in causing dismal clinical outcomes. Due to complex heterogeneity features of TNBC, identifying the biomarker associated to the chemoresistance remains a challenge. The emergence of the long non-coding RNA (lncRNA) as a potential signature may have proven to be a new deterrent to diagnostic and treatment options. Previous studies unveiled the associations of lncRNA in the development of TNBCs whereby the aggressiveness and response to therapies may be associated by the abrogation of the molecular mechanism lncRNA. Terminal differentiation induced ncRNA (TINCR) is a lncRNA which have been linked with many cancers including TNBC. The expression and behavior of TINCR may exert unfavorable outcome in TNBCs. Nevertheless, the underlying molecular mechanism of TINCR in driving chemoresistance in TNBC is not well understood. This review will highlight the potential molecular mechanisms of TINCR in TNBC chemoresistance and how it can serve as a future potential prognostic and therapeutic target for a better treatment intervention.

Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo.

Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.

Dietary Pattern, Genomic Stability and Relative Cancer Risk in Asian Food Landscape.

The incidence of cancer globally is increasing, partly due to lifestyle factors. Despite a better understanding of cancer biology and advancement in cancer management and therapies, current strategies in cancer treatment remain costly and cause socioeconomic burden especially in Asian countries. Hence, instead of putting more efforts in searches for new cancer cures, attention has now shifted to understanding how to mitigate cancer risk by modulating lifestyle factors. It has been established that carcinogenesis is multifactorial, and the important detrimental role of oxidative stress, chronic inflammation, and genomic instability is evident. To date, there is no study linking dietary pattern and genomic stability in cancer risk in the Asian food landscape. Thus, this present review article discusses recent literature on dietary pattern and genomic stability and its relationship with cancer risk in Asia.

The effects of polyphenols-rich tropical fruit juice on cognitive function and metabolomics profile - a randomized controlled trial in middle-aged women.

Objectives: Polyphenols, particularly anthocyanins, have received attention in improving health issues during old age, including decline in cognitive function and other health parameters. We aimed to determine the effects of polyphenols-rich tropical fruit TP 3-in-1™ juice towards improving cognitive function, oxidative stress and metabolomics profiles among middle-aged women.Methods: This clinical trial involved 31 subjects with signs of poor cognitive function, as assessed using the Rey Auditory Verbal Learning Test (RAVLT). They were randomized to receive either TP 3-in-1™ juice (n = 16) or placebo (n = 15). Study subjects consumed 500 ml of beverages for three times per day, three days per week, for a period of ten weeks. Juice supplementation provided 9135 mg GAE of total phenolic content and 194.1 mg cyanidin-3-glucoside of total anthocyanin monomer.Results: There was a significant interaction effects on RAVLT immediate recall (p < 0.05) and Comprehensive Trail Making Test (CTMT) Trail 4 (p < 0.05). Metabolomics analysis showed the presence of metabolites related to polyphenols intake and cognitive functions with the intervention group showed increased urinary excretion of thyroxine and 3-methyladenine. Thyroxine and 3-methyladenine give stability to human transthyretin (TTR) and activate autophagy, respectively, which are associated with the pathogenesis of Alzheimer's disease.Conclusion: The result shows the potential of TP 3-in-1™ juice which is rich in anthocyanins in improving cognitive function, particularly learning, memory, processing speed, sequencing, mental flexibility and visual-motor skills domains, among middle-aged women.

A Cell-Based Systematic Review on the Role of Annexin A1 in Triple-Negative Breast Cancers.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as "Annexin A1" or "Lipocortin 1" and "Breast cancer" or "TNBC". A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-ß signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.

Synthesis, spectral characterization and antiproliferative activity of new organotin (IV) dithiocarbamate compounds on K562 cells.

Four new organotin(IV) dithiocarbamate compounds with general formulae of PhnSn [S2CN(CH2CH2OCH2CH3)]4-n for compound 1 and 2; and PhnSn[S2CN(CH3)(CH2CH2C6H5)]4-n for compound 3 and 4 were successfully synthesized via in situ insertion method. These compounds namely, diphenyltin(IV)- [1] and triphenyltin(IV) N,N-bis(2-ethoxyethyl)dithiocarbamate [2], diphenyltin(IV)- [3] and triphenyltin(IV) N-methyl-N-phenethyldithiocarbamate [4] were each characterized with CHNS elemental analysis, FT-IR and NMR spectroscopies (1H, 13C and 119Sn). The compounds were then assessed for their cytotoxicity against K562 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay upon 24 h treatment. All compounds produced the essential IR absorption bands and displayed important NCS2 peak in 13C NMR spectroscopy. From the cytotoxicity studies using MTT assay, the compounds were shown to inhibit cell proliferation in K562 leukemic cells with IC50 values ranging from 1.48 to 4.52 µM, and in the manners more cytotoxic compared to standard used imatinib.

Neuroimaging Functional Magnetic Resonance Imaging Task-Based Dorsolateral Prefrontal Cortex Activation Following 12 Weeks of Cosmos caudatus Supplementation Among Older Adults With Mild Cognitive Impairment.

BACKGROUND: Cosmos caudatus (CC) is traditional Asian vegetable, commonly consumed among the Southeast Asian population. It has been reported to be high in flavonoids and might potentially improve brain activity among older adults with mild cognitive impairment (MCI). The effect of CC in brain activation improvement using neuroimaging is yet to be discovered. PURPOSE: To investigate the effects of CC supplement on brain activity using functional magnetic resonance imaging (fMRI) among older adults with MCI. STUDY TYPE: Prospective, randomized, double-blind, placebo-controlled trial. POPULATION/SUBJECTS: Twenty older adults with mild cognitive impairment (60-75 years old), 14 of them (70%) were female subjects. FIELD STRENGTH/SEQUENCE: A 3.0-T, T1-weighted anatomical images, T2*-weighted imaging data, A single shot, gradient echo-echo planar imaging (EPI) sequence. ASSESSMENT: All subjects were asked to consume two 500 mg capsules of either CC supplement or placebo (maltodextrin) daily for 12 weeks. Cognitive function was measured using validated neuropsychological tests (i.e. Mini-mental State Examination and Digit Span) and task-based fMRI (N-back and Stroop Color Word Test) at baseline and 12th week. Brodmann's area 9, 46 and anterior cingulate cortex were selected as the regions of interest to define dorsolateral prefrontal cortex (DLPFC) in fMRI analysis. STATISTICAL TESTS: Normality test was performed with the Shapiro-Wilk test. Two-way repeated ANOVA determined the intervention effects of the CC supplementation on brain activity after adjustments for covariates. Significance level at P < 0.05 for independent-t test and Chi square test; adjusted P < 0.0042 for two-way repeated ANOVA after Bonferroni correction. RESULTS: Findings showed significant improvements in digit span (partial η2  = 0.559), increment in right DLPFC activation while performing 1-back task (partial η2  = 0.586) and left DLPFC activation while performing Stroop Color Word Test (SCWT) (congruent) task (partial η2  = 0.432) at 12th week of CC supplementation. CONCLUSION: CC supplementation might have the ability to improve DLPFC activation, potentially leading to improved working memory among older adults with MCI after 12 weeks of administration. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Incidence and multidimensional predictors of occasional and recurrent falls among Malaysian community-dwelling older persons.

BACKGROUND: Falls incidence rate and comprehensive data on factors that predict occasional and repeated falls from large population-based studies are scarce. In this study, we aimed to determine the incidence of falls and identify predictors of occasional and recurrent falls. This was done in the social, medical, physical, nutritional, biochemical, cognitive dimensions among community-dwelling older Malaysians. METHODS: Data from 1,763 Malaysian community-dwelling older persons aged ≥ 60 years were obtained from the LRGS-TUA longitudinal study. Participants were categorized into three groups according to the presence of a single fall (occasional fallers), ≥two falls (recurrent fallers), or absence of falls (non-fallers) at an 18-month follow-up. RESULTS: Three hundred and nine (17.53 %) participants reported fall occurrences at an 18-month follow-up, of whom 85 (27.51 %) had two or more falls. The incidence rate for occasional and recurrent falls was 8.47 and 3.21 per 100 person-years, respectively. Following multifactorial adjustments, being female (OR: 1.57; 95 % CI: 1.04-2.36), being single (OR: 5.31; 95 % CI: 3.36-37.48), having history of fall (OR: 1.86; 95 % CI: 1.19-2.92) higher depression scale score (OR: 1.10; 95 % CI: 1.02-1.20), lower hemoglobin levels (OR: 0.90; 95 % CI: 0.81-1.00) and lower chair stand test score (OR: 0.93; 95 % CI: 0.87-1.00) remained independent predictors of occasional falls. While, having history of falls (OR: 2.74; 95 % CI: 1.45-5.19), being a stroke survivor (OR: 8.57; 95 % CI: 2.12-34.65), higher percentage of body fat (OR: 1.04; 95 % CI: 1.01-1.08) and lower chair stand test score (OR: 0.87; 95 % CI: 0.77-0.97) appeared as recurrent falls predictors. CONCLUSIONS: Having history of falls and lower muscle strength were predictors for both occasional and recurrent falls among Malaysian community-dwelling older persons. Modifying these predictors may be beneficial in falls prevention and management strategies among older persons.

Cognitive frailty is a robust predictor of falls, injuries, and disability among community-dwelling older adults.

BACKGROUND: Cognitive frailty, a combination of physical frailty and cognitive impairment, is associated with functional decline in older adults. However, there is limited information if cognitive frailty predicts the incidence of falls, injuries, and disability. In this study, we aimed to determine the ability of cognitive frailty in predicting the incidence of falls, injuries and disability among multi-ethnic older adults in Malaysia at 5 years follow-up. METHODS: In this prospective cohort study, a total of 400 participants aged 60 years and above were successfully followed up at 5 years. Participants' socio-demographic, medical history, psycho-social, physical, cognitive and dietary intake information was obtained. Cognitive frailty was defined as comorbid physical frailty (> 1 Fried criteria) and mild cognitive impairment (Petersen criteria). Univariate analysis was performed for all variables, followed by hierarchical binary logistic regression (BLR) analysis to identify the ability of CF in predicting the incidence of falls, injuries, and disability. The significant value was set at p < 0.05. RESULTS: Cognitive frailty was found to be associated with greater risk of adverse consequences after adjusting for covariates. Both cognitive frailty (Adjusted Odd ratio (Adj OR) = 2.98, 95% confidence interval (CI): 1.78-4.99, p < 0.05) and physical frailty (Adj OR = 2.88, 95% CI: 1.19-6.99, p < 0.05) were significant predictors of incidence of falls. Risk of injuries was also significantly increased with the presence of cognitive frailty (Adj OR = 3.06, 95% CI: 1.23-7.60, p < 0.05) and physical frailty (Adj OR = 3.04, 95% CI: 1.75-5.28, p < 0.05). In addition, cognitive frailty (Adj OR = 5.17, 95% CI: 1.11-24.21, p < 0.05) and physical frailty (Adj OR = 4.99, 95% CI: 1.11-22.57, p < 0.05) were shown to significantly predict the incidence of disability among older adults. CONCLUSION: Cognitive frailty is a robust predictor of falls, injuries, and disability in older adults. Possible early multi-domain preventive and management strategies of cognitive frailty that contribute to adverse consequences are required to decrease further functional decline and promote independence in older adults.

Antimutagenic, Cytoprotective and Antioxidant Properties of Ficus deltoidea Aqueous Extract In Vitro.

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5-100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

The Roles of Tissue Rigidity and Its Underlying Mechanisms in Promoting Tumor Growth.

Tissues become more rigid during tumorigenesis and have been identified as a driving factor for tumor growth. Here, we highlight the concept of tissue rigidity, contributing factors that increase tissue rigidity, and mechanisms that promote tumor growth initiated by increased tissue rigidity. Various factors lead to increased tissue rigidity, promoting tumor growth by activating focal adhesion kinase (FAK) and Rho-associated kinase (ROCK). Consequently, result in recruitment of cancer-associated fibroblasts (CAFs), epithelial-mesenchymal transition (EMT) and tumor protection from immunosurveillance. We also discussed the rationale for targeting tumor tissue rigidity and its potential for cancer treatment.

Prevalence of Poor Mental Health and Cognitive Status among Middle-Aged Adults and Its Predictors in Relation to Polyphenols Intake.

BACKGROUND: Decline in mental health and cognitive status starts to show its sign during middle-age and is affected by dietary factors, namely the polyphenols intake. Polyphenols have received attention in improving health issues related to aging, including decline in mental health and cognitive. The aim of this study is to determine the prevalence of poor mental health and cognitive status among middle-aged adults and its predictors in relation to polyphenols intake. METHODS: Subjects' food intakes were calculated by using dietary history questionnaire and food frequency questionnaire for polyphenols. The subjects' mental health and cognitive status were measured by general health questionnaire-28 (GHQ-28) and Rey's auditory verbal learning test (RAVLT). RESULTS: More than 40% of middle-aged adults were identified as having signs of poor mental health. A total of 67.9% of the subjects had poor cognitive status according to RAVLT immediate recall. Hierarchical binary logistic regression indicated that fat intake was associated with somatic symptoms for both men [adjusted odds ratio (AOR) = 1.04; P < 0.05] and women (AOR = 1.06; P < 0.05). Intake of lignan (AOR = 1.071; P < 0.05) was associated with better RAVLT immediate recall among women. Additionally, high cholesterol (AOR = 3.14; P < 0.05) was associated with poor score of RAVLT delayed recall for women. CONCLUSIONS: Early detection of poor mental health and cognitive is crucial to prevent Alzheimer's disease in old age.

Water extract of Clinacanthus nutans leaves exhibits in vitro, ex vivo and in vivo anti-angiogenic activities in endothelial cell via suppression of cell proliferation.

BACKGROUND: Clinacanthus nutans (Burm. f.) Lindau. has traditionally been using in South East Asia countries to manage cancer. However, scientific evidence is generally lacking to support this traditional claim. This study aims to investigate the in vitro, ex-vivo and in vivo effects of C. nutans extracts on angiogenesis. METHODS: C. nutans leaves was extracted with 50-100% ethanol or deionised water at 1% (w/v). Human umbilical veins endothelial cell (HUVEC) proliferation was examined using MTT assay. The in vitro anti-angiogenic effects of C. nutans were assessed using wound scratch, tube formation and transwell migration assays. The VEGF levels secreted by human oral squamous cell carcinoma (HSC-4) cell and HUVEC permeability were also measured. Besides, the rat aortic ring and chick embryo chorioallantoic membrane (CAM) assays, representing ex vivo and in vivo models, respectively, were performed. RESULTS: The MTT assay revealed that water extract of C. nutans leaves exhibited the highest activity, compared to the ethanol extracts. Therefore, the water extract was chosen for subsequent experiments. C. nutans leaf extract significantly suppressed endothelial cell proliferation and migration in both absence and presence of VEGF. However, the water extract failed to suppress HUVEC transmigration, differentiation and permeability. C. nutans water extract also did not suppress HSC-4 cell-induced VEGF production. Importantly, C. nutans water extract significantly abolished the sprouting of vessels in aortic rings as well as in chick embryo CAM. CONCLUSION: In conclusion, these findings reveal potential anti-angiogenic effects of C. nutans, providing new evidence for its potential application as an anti-angiogenic agent.

Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults.

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.

Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e(+) cells but reduced the total counts of Sca-1(+), CD11b(+), Gr-1(+), and CD45(+) cells at 7 and 12 µM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5µM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12µM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage.

Gelam honey attenuated radiation-induced cell death in human diploid fibroblasts by promoting cell cycle progression and inhibiting apoptosis.

BACKGROUND: The interaction between ionizing radiation and substances in cells will induce the production of free radicals. These free radicals inflict damage to important biomolecules such as chromosomes, proteins and lipids which consequently trigger the expression of genes which are involved in protecting the cells or repair the oxidative damages. Honey has been known for its antioxidant properties and was used in medical and cosmetic products. Currently, research on honey is ongoing and diversifying. The aim of this study was to elucidate the role of Gelam honey as a radioprotector in human diploid fibroblast (HDFs) which were exposed to gamma-rays by determining the expression of genes and proteins involved in cell cycle regulation and cell death. METHODS: Six groups of HDFs were studied viz. untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/ml of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma-rays at the dose rate of 0.25 Gy/min. RESULTS: Our findings showed that, gamma-irradiation at 1 Gy up-regulated ATM, p53, p16ink4a and cyclin D1 genes and subsequently initiated cell cycle arrest at G0/G1 phase and induced apoptosis (p < 0.05). Pre-treatment with Gelam honey however caused down regulation of these genes in irradiated HDFs while no significant changes was observed on the expression of GADD45 and PAK genes. The expression of ATM and p16 proteins was increased in irradiated HDFs but the p53 gene was translated into p73 protein which was also increased in irradiated HDFs. Gelam honey treatment however significantly decreased the expression of ATM, p73, and p16 proteins (p < 0.05) while the expression of cyclin D1 remained unchanged. Analysis on cell cycle profile showed that cells progressed to S phase with less percentage of cells in G0/G1 phase with Gelam honey treatment while apoptosis was inhibited. CONCLUSION: Gelam honey acts a radioprotector against gamma-irradiation by attenuating radiation-induced cell death.

Involvement of Seladin-1 in goniothalamin-induced apoptosis in urinary bladder cancer cells.

BACKGROUND: Selective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer's disease. Interestingly, the expression of this protein is upregulated in several cancers, including primary bladder cancer. However, its role in cancer formation has yet to be discovered. Goniothalamin is a natural product that has been demonstrated to induce apoptosis in various cancer cell lines. In this study, we have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4. METHODS: The cytotoxicity of goniothalamin in human urinary bladder cancer cell line RT4 was assessed using MTT assay and the mode of cell death was determined by Annexin V-FITC/PI labeling assay. Finally, the expression of Seladin-1 protein in goniothalamin-treated RT4 cells was determined by Western blot. RESULTS: MTT assay showed that the cytotoxicity of goniothalamin on RT4 cells was concentration and time dependent with IC50 values of 61 µM (24 hr), 38 µM (48 hr) and 31 µM for 72 hr, respectively. Cell death induced was confirmed through apoptosis; as assessed using the Annexin V-FITC/PI labeling assay. Furthermore, the involvement of Seladin-1 in goniothalamin-induced apoptosis was evidenced through the cleavage of 60 kDa protein to 40 kDa and 20 kDa. This was followed by a gradual increase of 20 kDa fragment suggesting the involvement of Seladin-1 in goniothalamin-induced apoptosis on RT4 cells. CONCLUSION: This study demonstrates that goniothalamin induce cytotoxicity and apoptosis on RT4 cells. The involvement of Seladin-1 in goniothalamin-induced apoptosis further suggested that Seladin-1 may play a role in the formation of primary bladder cancer.

The role of Hibiscus sabdariffa L. (Roselle) in maintenance of ex vivo murine bone marrow-derived hematopoietic stem cells.

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.

Cellular and DNA Toxicity Study of Triphenyltin Ethyl Phenyl Dithiocarbamate and Triphenyltin Butyl Phenyl Dithiocarbamate on K562, Leukemia Cell Line.

INTRODUCTION: Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell). METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes. RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 µM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 µM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects. CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.