Relationship of metabolic syndrome defined by IDF or revised NCEP ATP III with glycemic control among Malaysians with Type 2 Diabetes.

BACKGROUND: The chronic complications of Type 2 Diabetes (T2D) such as macrovascular disease is amplified with the increase in the number of metabolic syndrome (MetS) risk factors. This research aims to study the relationship of MetS, diagnosed by the International Diabetes Federation (IDF) or revised National Cholesterol Education Programs Adult Treatment Panel III (NCEP ATP III) criteria, with glycemic control, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), C-peptide, and insulin resistance in T2D patients. METHODS: The study is a cross-sectional observational study which, involved 485 T2D patients who are receiving treatment at the University Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. The MetS among the T2D patients was diagnosed based on IDF and revised NCEP ATP III criteria. C-peptide and HbA1c levels were determined by an automated quantitative immunoassay analyzer and high-performance liquid chromatography, respectively. The MetS factors; FBG, triglyceride, and high-density lipoprotein cholesterol were measured by spectrophotometer. RESULTS: Application of the IDF and revised NCEP ATP III criteria respectively resulted in 73% and 85% of the T2D subjects being diagnosed with MetS. The concordance of these criteria in diagnosing MetS among T2D patients was low (κ = 0.33, P < 0.001). Both IDF and revised NCEP ATP III criteria indicated that T2D patients with 5 MetS factors had higher insulin resistance (P = 2.1 × 10-13; 1.4 × 10-11), C-peptide (P = 1.21 × 10-13; 4.1 × 10-11), FBG (P = 0.01; 0.021), and HbA1c (P = 0.039; 0.018) than those T2D patients without MetS, respectively. CONCLUSION: Although there is a low concordance between IDF and revised NCEP ATP III criteria in the diagnosis of MetS among T2D patients, both criteria showed that T2D patients with 5 MetS factors had higher insulin resistance, C-peptide, FBG, and HbA1c.

High sPLA2-IIA level is associated with eicosanoid metabolism in patients with bacterial sepsis syndrome.

The aim of this study was to determine the association between secretory phospholipase A2 group IIA (sPLA2-IIA) and eicosanoid pathway metabolites in patients with bacterial sepsis syndrome (BSS). Levels of sPLA2-IIA, eicosanoids prostaglandin (PG)E2, PGD synthase were quantified in the sera from patients confirmed to have bacterial sepsis (BS; N = 45), bacterial severe sepsis/septic shock (BSS/SS; N = 35) and healthy subjects (N = 45). Cyclooxygenase (COX)-1 and COX-2 activities were analyzed from cell lysate. Serum levels of sPLA2-IIA, PGE2, and PGDS increased significantly in patients with BS and BSS/SS compared to healthy subjects (p<0.05). COX-2 activity was significantly increased in patients with BS compared to healthy subjects (p<0.05), but not COX-1 activity. Binary logistic regression analysis showed that sPLA2-IIA and PGE2 were independent factors predicting BSS severity. In conclusion, high level of sPLA2-IIA is associated with eicosanoid metabolism in patients with BSS.

Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults.

OBJECTIVES: This study aims to compare the differential gene expression resulting from tocotrienol-rich fraction and α-tocopherol supplementation in healthy older adults. METHODS: A total of 71 eligible subjects aged 50 to 55 years from Gombak and Kuala Lumpur, Malaysia, were divided into three groups and supplemented with placebo (n=23), α-tocopherol (n=24) or tocotrienol-rich fraction (n=24). Blood samples were collected at baseline and at 3 and 6 months of supplementation for microarray analysis. RESULTS: The number of genes altered by α-tocopherol was higher after 6 months (1,410) than after 3 months (273) of supplementation. α-Tocopherol altered the expression of more genes in males (952) than in females (731). Similarly, tocotrienol-rich fraction modulated the expression of more genes after 6 months (1,084) than after 3 months (596) and affected more genes in males (899) than in females (781). α-Tocopherol supplementation modulated pathways involving the response to stress and stimuli, the immune response, the response to hypoxia and bacteria, the metabolism of toxins and xenobiotics, mitosis, and synaptic transmission as well as activated the mitogen-activated protein kinase and complement pathways after 6 months. However, tocotrienol-rich fraction supplementation affected pathways such as the signal transduction, apoptosis, nuclear factor kappa B kinase, cascade extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2, immune response, response to drug, cell adhesion, multicellular organismal development and G protein signaling pathways. CONCLUSION: Supplementation with either α-tocopherol or tocotrienol-rich fraction affected the immune and drug response and the cell adhesion and signal transduction pathways but modulated other pathways differently after 6 months of supplementation, with sex-specific responses.

Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults

OBJECTIVES This study aims to compare the differential gene expression resulting from tocotrienol-rich fraction and α-tocopherol supplementation in healthy older adults. METHODS A total of 71 eligible subjects aged 50 to 55 years from Gombak and Kuala Lumpur, Malaysia, were divided into three groups and supplemented with placebo (n=23), α-tocopherol (n=24) or tocotrienol-rich fraction (n=24). Blood samples were collected at baseline and at 3 and 6 months of supplementation for microarray analysis. RESULTS The number of genes altered by α-tocopherol was higher after 6 months (1,410) than after 3 months (273) of supplementation. α-Tocopherol altered the expression of more genes in males (952) than in females (731). Similarly, tocotrienol-rich fraction modulated the expression of more genes after 6 months (1,084) than after 3 months (596) and affected more genes in males (899) than in females (781). α-Tocopherol supplementation modulated pathways involving the response to stress and stimuli, the immune response, the response to hypoxia and bacteria, the metabolism of toxins and xenobiotics, mitosis, and synaptic transmission as well as activated the mitogen-activated protein kinase and complement pathways after 6 months. However, tocotrienol-rich fraction supplementation affected pathways such as the signal transduction, apoptosis, nuclear factor kappa B kinase, cascade extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2, immune response, response to drug, cell adhesion, multicellular organismal development and G protein signaling pathways. CONCLUSION Supplementation with either α-tocopherol or tocotrienol-rich fraction affected the immune and drug response and the cell adhesion and signal transduction pathways but modulated other pathways differently after 6 months of supplementation, with sex-specific responses.

Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of aging rat.

Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.

Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions.

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age.

Vitamin E, γ-tocotrienol, Protects Against Buthionine Sulfoximine-Induced Cell Death by Scavenging Free Radicals in SH-SY5Y Neuroblastoma Cells.

The induction of reactive oxygen species (ROS) to selectively kill cancer cells is an important feature of radiotherapy and various chemotherapies. Depletion of glutathione can induce apoptosis in cancer cells or sensitize them to anticancer treatments intended to modulate ROS levels. In contrast, antioxidants protect cancer cells from oxidative stress-induced cell death by scavenging ROS. The role of exogenous antioxidants in cancer cells under oxidative insults remains controversial and unclear. This study aimed to identify protective pathways modulated by γ-tocotrienol (γT3), an isomer of vitamin E, in human neuroblastoma SH-SY5Y cells under oxidative stress. Using buthionine sulfoximine (BSO) as an inhibitor of glutathione synthesis, we found that BSO treatment reduced the viability of SH-SY5Y cells. BSO induced cell death by increasing apoptosis, decreased the level of reduced glutathione (GSH), and increased ROS levels in SH-SY5Y cells. Addition of γT3 increased the viability of BSO-treated cells, suppressed apoptosis, and decreased the ROS level induced by BSO, while the GSH level was unaffected. These results suggest that decreasing GSH levels by BSO increased ROS levels, leading to apoptosis in SH-SY5Y cells. γT3 attenuated the BSO-induced cell death by scavenging free radicals.

Significant association between parathyroid hormone and uric acid level in men.

BACKGROUND: Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH) and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men. METHODS: A cross-sectional study was conducted among 380 Malay and Chinese men aged 20 years and above, residing in the Klang Valley, Malaysia. Their body anthropometry was measured, and their fasting blood samples were collected for biochemical analysis. The relationship between PTH and uric acid was analyzed using regression analysis. RESULTS: Increased serum PTH level was significantly associated with increased serum uric acid level (ß=0.165; P=0.001). Increased PTH level was also significantly associated with the condition of hyperuricemia in the study population (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.017-1.075; P=0.002). All analyses were adjusted for age, body mass index, vitamin D, total calcium, inorganic phosphate, blood urea nitrogen and creatinine levels. CONCLUSION: There is a significant positive relationship between PTH level and uric acid level in Malaysian men. This relationship and its clinical significance should be further investigated in a larger longitudinal study.

γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells.

Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.

Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells.

BACKGROUND: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. METHODS: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. RESULTS: The results of MTS assay showed that the IC50 of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC50 of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of < 1, suggesting synergism. Cell death in response to the combined ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. CONCLUSIONS: In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.

Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy.

Glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death. We screened 14 patients from 13 families with clinical and biochemical features suggestive of GCE for mutation in AMT, GLDC and GCSH genes by direct sequencing and genomic rearrangement of GLDC gene using a multiplex ligation-dependant probe amplification. We identified mutations in all 14 patients. Seven patients (50%) have biallelic mutations in GLDC gene, six patients (43%) have biallelic mutations in AMT gene and one patient (7%) has mutation identified in only one allele in GLDC gene. Majority of the mutations in GLDC and AMT were missense mutations and family specific. Interestingly, two mutations p.Arg265His in AMT gene and p.His651Arg in GLDC gene occurred in the Penan sub-population. No mutation was found in GCSH gene. We concluded that mutations in both GLDC and AMT genes are the main cause of GCE in Malaysian population.

Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells.

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.

Vitamin E in sarcopenia: current evidences on its role in prevention and treatment.

Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS) can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies.

Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells.

The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.

The relationships between thyroid hormones and thyroid-stimulating hormone with lipid profile in euthyroid men.

BACKGROUND AND AIM: Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population. METHODS: A total of 708 Chinese and Malay men aged 20 years and above were recruited in this cross-sectional study. Their blood was collected for the determination of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free thyroxine (FT4), free triiodothyronine (FT3) and TSH levels. The association was analyzed using multiple regression and logistic regression models with adjustment for age, ethnicity, body mass index and FT4/FT3/TSH levels. RESULTS: In multiple regression models, TSH was positively and significantly associated with TG (p<0.05). Free T4 was positively and significantly associated with TC, LDL-C and HDL-C (p<0.05). Free T3 was negatively and significantly associated with HDL-C (p<0.05). In binary logistic models, an increase in TSH was significantly associated with higher prevalence of elevated TG in the subjects (p<0.05), while an increase in FT4 was significantly associated with higher prevalence of elevated TC but a lower prevalence of subnormal HDL in the subjects (p<0.05). Free T3 was not associated with any lipid variables in the logistic regression (p>0.05). CONCLUSIONS: In euthyroid Malaysian men, there are positive and significant relationships between TSH level and TG level, and between FT4 level and cholesterol levels.

Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men.

BACKGROUND AND AIM: Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men. METHODS: A total of 373 men from the Malaysian Aging Male Study were included in the analysis. Data on subjects' demography, body mass index (BMI), body fat (BF) mass, waist circumference (WC), serum osteocalcin and fasting lipid levels were collected. Bioelectrical impendence (BIA) method was used to estimate BF. Multiple linear and binary logistic regression analyses were performed to analyze the association between serum osteocalcin and the aforementioned variables, with adjustment for age, ethnicity and BMI. RESULTS: Multiple regression results indicated that weight, BMI, BF mass, BF %, WC were significantly and negatively associated with serum osteocalcin (p < 0.001). There was a significant positive association between serum osteocalcin and high density lipoprotein (HDL) cholesterol (p = 0.032). Binary logistic results indicated that subjects with low serum osteocalcin level were more likely to be associated with high BMI (obese and overweight), high BF%, high WC and low HDL cholesterol (p < 0.05). Subjects with high osteocalcin level also demonstrated high total cholesterol level (p < 0.05) but this association was probably driven by high HDL level. These variables were not associated with serum C-terminal of telopeptide crosslinks in the subjects (p > 0.05). CONCLUSION: Serum osteocalcin is associated with indices of obesity and HDL level in men. These relationships should be validated by a longitudinal study, with comprehensive hormone profile testing.

Reversal of myoblast aging by tocotrienol rich fraction posttreatment.

Skeletal muscle satellite cells are heavily involved in the regeneration of skeletal muscle in response to the aging-related deterioration of the skeletal muscle mass, strength, and regenerative capacity, termed as sarcopenia. This study focused on the effect of tocotrienol rich fraction (TRF) on regenerative capacity of myoblasts in stress-induced premature senescence (SIPS). The myoblasts was grouped as young control, SIPS-induced, TRF control, TRF pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological observation, activity of senescence-associated ß-galactosidase (SA-ß-galactosidase), and cell proliferation were determined. 50 µg/mL TRF treatment exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit large flattened cells and prominent intermediate filaments (senescent-like morphology). The activity of SA-ß-galactosidase was significantly increased, but the proliferation capacity was significantly reduced as compared to young control. The activity of SA-ß-galactosidase was significantly reduced and cell proliferation was significantly increased in the posttreatment group whereas there was no significant difference in SA-ß-galactosidase activity and proliferation capacity of pretreatment group as compared to SIPS-induced myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts aging through replenishing the regenerative capacity of the cells. However, further investigation on the mechanism of TRF in reversing the myoblast aging is needed.

Improvement of metabolic parameters in healthy older adult men following a fasting calorie restriction intervention.

OBJECTIVE: Calorie restriction and intermittent fasting are two dietary interventions that can improve aging. Religious fasting also suggested having similar benefit; however, such studies are still scarce. Thus, this study aimed to determine the effect of fasting calorie restriction (FCR) on metabolic parameters and DNA damage among healthy older adult men. METHODS: A randomized controlled study was done on men, aged 50-70 years in Klang Valley, Malaysia. Subjects were divided into two groups; FCR (reduction of 300-500 kcal/d combined with 2 days/week of Muslim Sunnah Fasting) and control. Assessment was ascertained at three time point; baseline, weeks 6 and 12. Blood samples were analyzed for lipid profile, DNA damage and malondialdehyde (MDA). RESULTS: The FCR group reduced their energy intake for approximately 18% upon completion of the study. A significant interaction effect was found in body weight, body mass index, fat percentage, fat mass, blood pressure, total cholesterol, low-density lipoprotein cholesterol and the ratio of total cholesterol/high-density lipoprotein cholesterol (p < 0.05). A significant improvement (p < 0.001) in total DNA rejoining cells and MDA (p < 0.05) was also observed in the FCR group. CONCLUSION: FCR improved metabolic parameters and DNA damage in healthy older adult men. Therefore, there is a need to further examine the mechanism of FCR.

Thyroid-stimulating hormone is significantly associated with bone health status in men.

BACKGROUND AND AIM: Recent studies revealed a novel association between thyroid-stimulating hormone (TSH) and bone health status in healthy male populations. The present study aimed to validate this association and provide new information on the relationship between TSH levels and calcaneal speed of sound (SOS) in men. METHODS: This cross-sectional study recruited 681 men with complete data of calcaneal SOS, body anthropometry, serum TSH, free triiodothyronine (FT3) and free thyroxine (FT4) levels. RESULTS: All subjects had FT3 and FT4 levels within the in-house reference range and 13 subjects had lower than normal TSH levels. The results revealed that the SOS value of subjects was significantly associated with TSH after multiple adjustments (p<0.05). When subjects were divided into quintiles according to their TSH levels, the difference of SOS between men with low-normal TSH and high-normal TSH contributed significantly to the association between TSH and bone health status (p<0.05). The significance of the association persisted with the inclusion and exclusion of subclinical hyperthyroid subjects. CONCLUSIONS: There was a significant association between TSH levels and bone health status in men as assessed by quantitative ultrasound. This age-independent association between TSH and SOS might explain some of the individual variation of bone health status in men.