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In Taiwan, colorectal cancer (CRC) is the second most common cancer and the cancer with the third highest mortality rate. This may be because of the difficulty of detecting the disease in the early stages, as well as the fact that colonoscopy, a typical method used in screening for CRC, causes discomfort to the recipient and is prone to technical interference. For the earlier detection of CRC, finding an easier screening method with a simpler collection procedure is essential. Thus, in the present study, plasma samples from patients with CRC were analyzed to determine the extent of methylation in SHISA3 DNA. Studies have suggested that SHISA3, a newly identified tumor suppressor, can regulate tumor growth, and that the inactivation of its DNA can be traced to epigenomic alterations in CRC. Another study reported the presence of hypermethylated SHISA3 DNA in CRC biopsy specimens. In the present study, the plasma of 30 patients with CRC and nine healthy controls was collected and analyzed for the concentration of cell-free DNA through bisulfite sequencing. The methylation rates were determined. Our results have shown that an increasing amount of cell-free DNA in the group of CRC patient's plasma compared to the healthy group. Moreover, patients with later stages of CRC had higher concentrations of cell-free DNA. Notably, the methylation rate of SHISA3 was higher in the plasma of the CRC group than in that of the healthy group. The results indicated that the presence of tumor cells does not reduce the degree of SHISA3 DNA in the peripheral blood of patients with CRC. In other words, the hypermethylation of SHISA3, which inactivates the gene, is a potential cause of tumorigenesis. Furthermore, the methylation rate of SHISA3 DNA was higher in the plasma of patients with stage II CRC than in that of those with stage I CRC. In conclusion, the combination of conventional testing and screening for SHISA3 hypermethylation in plasma could improve the rate at which CRC is detected.

It has been established that prediabetes can causes significant comorbidities, particularly in the elderly. The deterioration of glucose metabolism are generally considered to be results of the impairment of the 4 factors: first, second insulin secretion (FPIS, SPIS, respectively), glucose effectiveness (GE), and insulin resistance. In this study, we enrolled older women to investigate their relationships with prediabetes. Five thousand four hundred eighty-two nonobese, nondiabetic women were included. They were divided into normal glucose tolerance and prediabetes groups. Receiver operating characteristic curve was performed to investigate the effects on whether to have prediabetes for each factors. Two models were built: Model 1: FPIS + SPIS, and Model 2: model 1 + GE. The area under the receiver operating characteristic (aROC) curve was used to determine the predictive power of these models. The aROC curve of GE was significantly higher than the diagonal line followed by SPIS and FPIS accordingly. The aROC curve of Model 1 (0.611) was not different from GE. However, Model 2 improved significantly up to 0.663. Based on this model, an equation was built (−0.003 × GE − 212.6 × SPIS − 17.9 × insulin resistance + 4.8). If the calculated value is equal or higher than 0 (≥0), then the subject has higher chance to have prediabetes (sensitivity = 0.607, specificity = 0.635). Among the 4 factors, GE is the most important contributor for prediabetes in older women. By building a model composed of FPIS, SPIS, and GE, the aROC curve increased significantly. The equation built from this model could predict prediabetes precisely.

In Taiwan, colorectal cancer (CRC) is the second most common cancer and the cancer with the third highest mortality rate. This may be because of the difficulty of detecting the disease in the early stages, as well as the fact that colonoscopy, a typical method used in screening for CRC, causes discomfort to the recipient and is prone to technical interference. For the earlier detection of CRC, finding an easier screening method with a simpler collection procedure is essential. Thus, in the present study, plasma samples from patients with CRC were analyzed to determine the extent of methylation in SHISA3 DNA. Studies have suggested that SHISA3, a newly identified tumor suppressor, can regulate tumor growth, and that the inactivation of its DNA can be traced to epigenomic alterations in CRC. Another study reported the presence of hypermethylated SHISA3 DNA in CRC biopsy specimens. In the present study, the plasma of 30 patients with CRC and nine healthy controls was collected and analyzed for the concentration of cell-free DNA through bisulfite sequencing. The methylation rates were determined. Our results have shown that an increasing amount of cell-free DNA in the group of CRC patient's plasma compared to the healthy group. Moreover, patients with later stages of CRC had higher concentrations of cell-free DNA. Notably, the methylation rate of SHISA3 was higher in the plasma of the CRC group than in that of the healthy group. The results indicated that the presence of tumor cells does not reduce the degree of SHISA3 DNA in the peripheral blood of patients with CRC. In other words, the hypermethylation of SHISA3, which inactivates the gene, is a potential cause of tumorigenesis. Furthermore, the methylation rate of SHISA3 DNA was higher in the plasma of patients with stage II CRC than in that of those with stage I CRC. In conclusion, the combination of conventional testing and screening for SHISA3 hypermethylation in plasma could improve the rate at which CRC is detected.

Patients with hepatocellular carcinoma (HCC) are prone to folate deficiency (FD). Here we showed that, in cell line-specific manner, FD caused resistance to FD-induced oxidative stress and multi-drug resistance (MDR). This resistance was due to upregulation of glucose-regulated protein 78 (GRP78) and Survivin. Using siRNA and Epigallocatechin gallate (EGCG), we found that GRP78 and Survivin cooperatively conferred MDR by decreasing FD-induced ROS generation. Our data showed that FD increases GRP78 and Survivin, which serve as ROS inhibitors, causing MDR in HCC. We suggest that folate supplementation may enhance the efficacy of chemotherapy.

Chitosan and Agaricus blazei Murill (ABM) extracts possess antitumor activities. The aim of the present study was to investigate whether chitosan, ABM extract or the two in combination were effective against tumors in tumor‑bearing mice. The mice were subcutaneously injected with SK-Hep 1 cells and were then were divided into the following six groups: Group 1, control group; group 2, chitosan 5 mg/kg/day; group 3, chitosan 20 mg/kg/day; group 4, ABM (246 mg/kg/day) and chitosan (5 mg/kg/day) combined; group 5, ABM (984 mg/kg/day) and chitosan (20 mg/kg/day) combined; and group 6, ABM (984 mg/kg/day). The mice were treated with the different concentrations of chitosan, ABM or combinations of the two for 6 weeks. The levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and vascular endothelial growth factor (VEGF), and tissue histopathological features were examined in the surviving animals. Based on the results of the investigation, the treatments performed in groups 2, 3 and 4 were identified as being capable of reducing the weights of the tumors, however, group 4, which was treated with chitosan (5 mg/kg/day) in combination with ABM (246 mg/kg/day) was able to reduce the levels of GOT and VEGF. As a result, treatment with chitosan in combination with ABM may offer potential in cancer therapy and requires further investigation.

Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features of MetS. The etiology of MetS is complex, involving both environmental and genetic factors. In this study, we examined the role of specific candidate genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D subjects aged 35-64 years were recruited. Waist circumstance, plasma triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure were measured to define MetS. Subjects were divided into 4 groups according to MetS components. Target genes involved in fibrotic and inflammatory processes, insulin and diabetes, cell growth and proliferation, and hypertension were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms (SNPs) were analyzed to evaluate their genetic association with MetS severity in T2D subjects. Univariate ordinal logistic regression using a dominant model (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP markers within 4 genes with genotypes associated with MetS risk. For the SNP genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R), and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the reference group. In addition, the CC genotype was comparable to the TT genotype for rs3777411. There was no gender-specific effect. In conclusion, our results suggest that among the Han Chinese population, several SNPs increase the risk of severe MetS in T2D subjects. Further study in a large population should be conducted.

Background: We aimed to investigate the relationship between liver function tests (LFTs) and metabolic syndrome (MetS) as several studies have shown positive correlations between some of the LFTs, including alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GT), and MetS but have not fully explored the same in the elderly. Owing to the progress in public health, the aging of the general population becomes a major issue. Design: We enrolled subjects aged over 60 years who underwent routine health checkups in a Health Screening Center after excluding subjects with a history of hepatitis B or C infection, excessive alcohol consumption, liver fibrosis, cirrhosis, acute hepatitis, diabetes, hypertension, dyslipidemia, cardiovascular disease, or receiving medications for these diseases. Finally, 9,282 participants were eligible for analysis. Statistical Analysis: All data were tested for normal distribution with the Kolmogorov-Smirnov test and for homogeneity of variances with the Levene's test. A t-test was used to evaluate the differences between the two groups. Univariate and multivariate regressions were used to observe correlations between different parameters. Receiver operating characteristic curves of each LFT were used to predict MetS. Areas under curves and 95% confidence interval were also estimated and compared. Results: With the exception of aspartate aminotransferase and γ-fetal protein, the results of LFTs, including total and direct bilirubin, alkaline phosphatase (ALP), ALT, and γ-GT, were altered in the group with MetS. Furthermore, the levels of γ-GT in men and ALP in women were independently associated with all MetS components and had the highest areas under receiver operating characteristic curves. Conclusion: Abnormal LFTs are highly correlated with MetS in the hepatitis-free elderly, with levels of γ-GT in men and ALP in women being the most important factors. LFTs may represent an auxiliary tool for the detection of MetS.

Background Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells. Methods In this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated. Results The results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 μM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death. Conclusions These results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.

Aims/Introduction How to measure insulin resistance (IR) accurately and conveniently is a critical issue for both clinical practice and research. In the present study, we tried to modify the β-cell function, insulin sensitivity, and glucose tolerance test (BIGTT) in patients with normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) by oral glucose tolerance test (OGTT) and metabolic syndrome (MetS) components. Materials and Methods There were 327 participants enrolled and divided into NGT or AGT. Data from 75% of the participants were used to build the models, and the remaining 25% were used for external validation. Steady-state plasma glucose (SSPG) concentration derived from the insulin suppression test was regarded as the standard measurement for IR. Five models were built from multiple regression: model 1 (MetS model with sex, age and MetS components); model 2 (simple OGTT model with sex, age, plasma glucose, and insulin concentrations at 0 and 120 min during OGTT); model 3 (full OGTT model with sex, age, and plasma glucose and insulin concentrations at 0, 30, 60, 90, 120, and 180 min during OGTT); model 4 (simple combined model): model 1 and model 2; and model 5 (full model): model 1 and 3. Results In general, our models had higher r2 compared with surrogates derived from OGTT, such as homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index. Among them, model 5 had the highest r2 (0.505 in NGT, 0.556 in AGT, respectively). Conclusions Our modified BIGTT models proved to be accurate and easy methods for estimating IR, and can be used in clinical practice and research.

The major contributors to the pathogenesis of type 2 diabetes are impaired insulin action and insulin secretion, including second phase insulin secretion (2nd ISEC). This study aimed to compare surrogates derived from the mixed meal tolerance test (MTT) with 2nd ISEC derived from modified low-dose graded glucose infusion (M-LDGGI) in patients with type 2 diabetes. We were subsequently able to decide which surrogate would be performed easily and accurately. Twenty type 2 diabetes patients were enrolled. They received both MTT and M-LDGGI. The standardized MTT meals were provided at 8:00 A.M. and 12:00 P.M. The M-LDGGI was a simplified version of the Polonsky method; only two 80-min stages of glucose infusion (2 and 6 mg/kg/min) were given. The slopes of the insulin to glucose curve during the test were regarded as the 2nd ISEC. First, we used the area under the insulin curve (AUC(IN)) during MTT to quantify the 2nd ISEC. The best correlated AUC(IN) was from 60-240 min. Second, the slopes between any two time points of the plasma insulin to glucose level (SLOPE(I/G)) were also assessed. The time period best correlated with 2nd ISEC was from 0-120 min (SLOPE₀₋₁₂₀). Finally, the insulin-to-glucose ratio (IGr) of each time point was used to estimate the 2nd ISEC, and the best correlation was observed at 180 min. In conclusion, estimating 2nd ISEC surrogates derived from MTT proved to be possible. The most accurate surrogate is the SLOPE₀₋₁₂₀, while IG(r180) is another less precise but more convenient method.

The concept of using single criterion of normal blood pressure with systolic blood pressure (SBP)

Summary Background With the growing number of elderly population in Taiwan and many other countries, the role of metabolic syndrome (MetS) has become more important recently. Although had been reported in different age groups, the relationship between platelet and MetS in the geriatric population still remains unknown. Methods We included 1187 Taiwanese males who were older than 65 years. In this study, we excluded individuals with abnormal platelet counts to reveal a more clear relation between platelet counts and MetS. Platelet counts were analyzed among patients with and without MetS. We divided platelet counts into four groups according to quartiles arbitrary of platelet counts (lowest, PC1; highest, PC4). The number of MetS components was compared between platelet groups with analysis of variance. We also used simple correlation and multivariate linear regression to find the relationship between platelet counts and MetS components. Results We found that the platelet counts were higher in the group with MetS but not significantly different ( p = 0.675). The fasting plasma glucose (FPG), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), and Log-triglyceride (Log-TG) were all statistically different across the four platelet groups. These four components were also positively correlated to platelet count in simple correlation. Not surprisingly, FPG, LDL-C, TG, and Log-TG were positively correlated with platelet count in multivariate linear regression. Conclusion FPG, LDL-C, TG, and Log-TG were positively correlated with platelet count among the MetS components in geriatric Taiwanese males. The role of HDL-C and LDL-C in the definition of MetS should be re-evaluated.

Aim The present study evaluated the relative influence of body mass index (BMI) on insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) at a fixed fasting plasma glucose level in an older ethnic Chinese population. Methods In total, 265 individuals aged 60 years with a fasting plasma glucose level of 5.56 mmol/L were enrolled. Participants had BMIs of 20.0–34.2 kg/m2. IR, FPIS, SPIS, and GE were estimated using our previously developed equations. Pearson correlation analysis was conducted to assess the correlations between the four diabetogenesis factors and BMI. A general linear model was used to determine the differences in the percentage of change among the four factor slopes against BMI. Results Significant correlations were observed between BMI and FPIS, SPIS, IR, and GE in both women and men, which were higher than those reported previously. In men, BMI had the most profound effect on SPIS, followed by IR, FPIS, and GE, whereas in women, the order was slightly different: IR, followed by FPIS, SPIS, and GE. Significant differences were observed among all these slopes, except for the slopes between FPIS and SPIS in women (p = 0.856) and IR and FPIS in men (p = 0.258). Conclusions The contribution of obesity to all diabetes factors, except GE, was higher than that reported previously. BMI had the most profound effect on insulin secretion in men and on IR in women in this 60-year-old cohort, suggesting that lifestyle modifications for obesity reduction in women remain the most important method for improving glucose metabolism and preventing future type 2 diabetes mellitus.

To evaluate the association of The study is to evaluate the association of metabolic syndrome (MS) and its components on brachial-ankle pulse wave velocity (baPWV), an indirect marker of subclinical atherosclerosis, in middle-aged Taiwanese males. A total of 442 men aged 40 to 65 years were included in this cross-sectional survey. Arterial stiffness was measured using a non-invasive method by baPWV. MS is defined by the presence of ≥ 3 components using the modified National Cholesterol Education Program criteria. The mean baPWV was 1478.6 and 1520.3 cm/sec in normal-weight and overweight adults, respectively. Age, systolic blood pressure (BP), diastolic BP, and fasting blood glucose (FBG) correlated with baPWV levels in normal-weight and overweight males. In multiple logistic regression analysis, after adjusting for potential confounders, MS and its components (such as high BP and high FBG) were significantly associated with abnormal baPWV (≥1400 cm/sec) (p < 0.001). MS and its components are significantly associated with abnormal baPWV in Taiwanese middle-aged males and in addition, high BP was the component of MS most significantly associated with abnormal baPWV.

Background: Hyperglycemia increases prevalence of metabolic syndrome (MetS), type 2 diabetes (T2D) and cardiovascular disease (CVD). But the role of normoglycemia on the development of T2D and CVD in elderly population remains unclear. Aim: To determine an optimal cut-off for fasting plasma glucose (FPG) to predict MetS and subsequent risk of T2D and CVD in an elderly Taiwanese population with normal FPG levels. Design: Two stages included cross-sectional (Stage 1) and prospective (Stage 2) cohort study. Methods: In Stage 1 18 287 subjects aged ≥60 years were enrolled; of these, 5039 without T2D and CVD advanced to Stage 2 and a mean follow-up of 3.8 years. MetS components were analysed, and in Stage 1, FPG cut-offs for MetS risk were calculated using receiver operating characteristic (ROC) curve analyses. In Stage 2, subjects without T2D and CVD in Stage 1 were classified into high-FPG and low-FPG groups based on cut-offs, and sex specific differences in incidence for T2D and CVD were calculated. Results: ROC curve analysis gave an optimal FPG cut-off for MetS of 93 mg/dl and 92 mg/dl for males and females, respectively. The high-FPG group had a 1.599- and 1.353-fold higher chance of developing T2D compared with the low-FPG group for males and females, respectively (95% CI: 1.606–2.721 and 1.000–1.831, P = 0.015 and 0.05). The high-FPG group had a 1.24-fold higher chance of developing CVD for females (95% CI: 1.015–1.515, P = 0.035); however, there was no difference for males. Conclusions: Our results suggest that FPG within the normal range was associated with MetS, and elderly subjects with high normal levels have a higher incidence of developing T2D for both sexes, and CVD for females, over the short-term.

Background Metabolic syndrome’s (MetS) role in predicting cardiovascular diseases and diabetes has been confirmed in many large cohort studies. Nontraditionally, hematogram components are significantly related to MetS in many different age groups. However, little is known about its role among the elderly. Methods We enrolled 18,907 subjects over the age of 65 years who underwent regular health examinations. They were divided into three groups according to age: young old (YO: ≥ 65 and

Summary Introduction It is well known that higher fasting plasma glucose (FPG) is associated with metabolic syndrome (MetS). This relationship still exists even the FPG is within the normal range. However, most of these studies did not exclude subjects who were on medications which would affect the results of the studies. At the same time, there is no longitudinal study done to validate this correlation, especially in elderly. In this study, the relationships between normal FPG and MetS were evaluated. Method We randomly selected 57,517 subjects who were ≥ 60-years old from health screening centre. In the first part of study, subjects were enrolled in the cross-sectional study to find out the optimal cut-off value of FPG with higher chances to have MetS. In the second part of current study, subjects with MetS at baseline were excluded from the same study group, and performed a median 5.3-year longitudinal study. Results There were 18,287 subjects enrolled in this study. In the first part of study, the cross-sectional study, optimal cut-off values of FPG were determined by the ROC curve and the sensitivity for these cut-off values were 56.6% in men and 60.9% in women, respectively. The result showed that lower FPG is healthier than the higher (log-rank test, p

Hypertension and prehypertension can increase the risk of developing cardiovascular disease (CVD) and diabetes. However, whether the harmful effects of high blood pressure (BP) are also seen with high normotension remains unknown. This 10-year longitudinal follow-up study aimed to investigat

Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects, including antiproliferative and anticarcinogenic activities, in several cancers. In the present study, we determined if deguelin would inhibit migration and invasion in U-2 OS human osteosarcoma cells. Deguelin significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells which was associated with a reduction of activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). Furthermore, results from western blotting indicated that deguelin decreased the cell proliferation and cell growth-associated protein levels, such as SOS1, PKC, Ras, PI3K, p-AKT(Ser473), IRE-1α, MEKK3, iNOS, COX2, p-ERK1/2, p-JNK1/2, p-p38, the cell motility and focal adhesion-associated protein levels, such as Rho A, FAK, ROCK-1, the invasion-associated protein levels, such as TIMP1, uPA, MMP-2. MMP-9, MMP-13, MMP-1 and VEGF in U-2 OS cells. Confocal microscopy revealed that deguelin reduced NF-κB p65, Rho A and ROCK-1 protein levels in cytosol. MMP-7, MMP-9 and Rho A mRNA levels were suppressed by deguelin. These in vitro results provide evidence that deguelin may have potential as a novel anti-cancer agent for the treatment of osteosarcoma and provides the rationale for in vivo studies in animal models.

The white blood cell (WBC) count was one of the first inflammatory markers associated with metabolic syndrome (MetS). Recently, two longitudinal studies have demonstrated a cause and effect relationship between MetS and WBC counts among middle-aged adults. However, no study has used WBC cutoff values to predict MetS in the elderly.Subjects who underwent routine health checkups, and were above 60 years of age, were enrolled. All subjects were followed-up until they developed MetS or until 4 years from the date of entry, whichever came earlier. Of the 4539 subjects eligible for enrollment, 3428 subjects comprised the study group and 1111 subjects comprised the validation group.WBC counts were significantly different between subjects with and without MetS in both genders. Using the ROC curve, WBC cutoff values of 5.7 × 10(3)/µl in males and 5.0 × 10(3)/µl in females were associated with the increased risk of developing MetS (all p values0.001). Using these WBC cutoff values, the hazard ratio (HR) for females was significant in both the study group and validation group. However, the HR for males failed significance in the validation group. Kaplan-Meier plots and κ coefficients confirmed that the WBC cutoff value could predict development of MetS in women but not in men.The association between WBC count and MetS was gender specific. A WBC cutoff value greater than 5.0 10(3)/µl may predict the development of MetS in elderly women.

Objectives: Plasma lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. The purpose of this study is to evaluate the correlation of anthropometric measures, lipids and lipoprotein profiles and serum Lp(a) values among children in Taiwan. We will attempt to find parameters that will be able to predict Lp(a) levels in children. Design and methods: After a probability-proportional-to size, multi-stages sampling procedure, we randomly sampled 1500 schoolchildren from 10 schools in Taipei city. Anthropometric measures including body weight, body height, waist and hip circumference and skinfolds were measured. We used standard methods to measure serum total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 and B (ApoA1 and ApoB) and Lp(a) levels. We also calculated low density lipoprotein-cholesterol (LDL-C) and CHOL/HDL-C ratio (TCHR) by formula. Results: We sampled 1283 children (635 boys and 648 girls) with a mean age of 13.3 years (from 12 to 16 years) in this study. The mean and medium serum Lp(a) levels were 16.8 and 8.8 mg/dl among boys and 20.8 and 11.9 mg/dl among girls. Children in the highest quintile of Lp(a) (mean = 49.6 and 58.6 mg/dl for boys and girls, respectively) had higher CHOL, LDL-C, ApoB levels and TCHR than children in the lowest quintile (mean = 3.1 and 3.7 mg/dl for boys and girls, respectively). Lipids and lipoprotein profiles, such as CHOL, LDL-C, Apo-B and TCHR were positively correlated with Lp(a) levels in both genders. Furthermore, the children with Lp(a) levels greater than or equal to 30 mg/dl had higher CHOL, LDL-C and Apo-B levels when compared to children with Lp(a) levels less than 30 mg/dl. After adjusting for age, cigarette smoking, alcohol drinking, puberty development and heart rates, LDL-C and ApoB levels were significantly positively associated with Lp(a) levels while ApoA1 was negatively associated among boys. Among girls, only Apo-B was significantly positively associated with Lp(a) and TG was negatively associated with Lp(a) levels. Most importantly, none of the anthropometric measures were significantly correlated with Lp(a) levels. Conclusions: From this study, we found that lipids and lipoproteins profiles, rather than degree of adiposity as reflected by anthropometric measures, are significantly associated with serum Lp(a) levels among school children.

Antrodia cinnamomea is a natural component of some herbal medicines used for treatment of abdominal pain, hypertension and hepatocellular carcinoma in Taiwan and other countries. Subchronic oral toxicity studies of A. cinnamomea extracts in male and female BALB/c mice were performed to evaluate its safety. Three different concentrations of A. cinnamomea (16.67, 833.3 and 1666.67 mg/kg/day) were given orally to groups of mice (10 mice/dose) for 90 consecutive days. All animals survived to the end of the study, and there were no significant differences in body weight among the control and treatment groups. No significant differences were found in hematological and serum biochemical parameters among the control and treatment groups. No abnormalities of internal organs were observed in the treated groups.

According to the World Health Organization, Complementary and alternative medicine (CAM) is a comprehensive term referring to traditional medical treatments and various forms of indigenous medicines, also known as indigenous or folk medicine. Cancer patients often use CAM in the form of nutritional supplements, psychological techniques and natural medical approaches in the place of or in parallel to conventional medicine. The present study aimed to determine if Chitosan can inhibit lung metastasis and hepatoma formation, by studying xenograft of B16F10 melanoma cells in C57BL/6 mice and of Smmu 7721 cells in SCID mice, respectively. For the lung metastasis model, after a five-week treatment, the survival rates of B6 mice were 15% for the control group and 35%, 20%, 45% and 40% for the 320,000 kDa, 173,000 kDa, 86,000 kDa and 8,000 kDa molecular-weight treatment groups, respectively. Chitosan treatment dramatically increased lifespan and inhibited tumor metastasis especially in treatment groups of the low-molecular weight compound. For the hepatoma growth model, the size of the liver tumor mass was approximately14 mm in the control group. In comparison to the control group, the tumor mass grew slowly with Chitosan treatment, especially at the low-molecular weight treatment group. Chitosan slowed-down the rate of tumor growth but did not inhibit tumor formation. Data presented herein demonstrate that Chitosan has anticancer effects and thus further study of the substance is warranted to examine for mechanisms of action and optimal dosage.

Objective: Hematological parameters play a significant role in metabolic syndrome (MetS) and its development in the elderly, but the association and different ability of each parameter to predict MetS have not been investigated in the very old populations. Subjects and Methods: This cross-sectional and longitudinal study included 18,907 participants aged over 65 years and followed up until MetS development with a mean duration of 4 years from the entry date. MetS was diagnosed according to the latest harmonized criteria with modification for waist circumference. Correlations between hematological parameters and MetS were analyzed and operating characteristic curves were compared among each parameter. Stratification was conducted by gender and age as follows: young-old (65-74 years), old-old (75-84 years), and oldest-old (85-94 years). Results: White blood cell count (WBC) and hemoglobin (Hb) levels in both genders of young-old (65-74 years) and old-old (75-84 years) and platelet (PLT) in young-old (65-74 years) males were independent factors for risk of MetS. However, only WBC (P < 0.001) and Hb level (P < 0.001) in young-old (65-74 years) males and Hb level (P = 0.03) in old-old (75-84 years) females were independent factors of future MetS development. For predicting MetS, WBC and Hb levels were better markers than PLT in the old-old (75-84 years) and young-old (65-74 years) males group. In young-old (65-74 years) females, WBC was the most sensitive marker. Conclusions: Hematological parameters were associated with MetS, showing gender and age effects. These findings can be used for risk estimation of MetS development in the older population.

Neonatal alloimmune thrombocytopenia (NAIT) is a clinical syndrome that resembles hemolytic disease of the newborn, affecting the platelets only. The thrombocytopenia results from the maternal alloantibodies reacting with specific human platelet antigens (HPAs) on the fetal platelets. Forty-four maternal plasma samples were screened for platelet alloantibodies using qualitative solid phase enzyme-linked immunosorbent assay (ELISA) commercial kit (LIFECODES Pakplus, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA), and both the maternal and the corresponding cord blood samples were genotyped (LIFECODES ThromboType, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA). HPA genotyping results correlated with the genetic frequencies in the Taiwan population. A total of 34 newborns (77.3%) had partial HPA genotyping mismatches with the corresponding mothers. The most common partial mismatches between mothers and neonates in HPA genotypes were 13 (29.5%) in both HPA-3b and HPA-15a, followed by 12 (27.3%) in HPA-15b, and 8 (18.2%) in HPA-3a. The frequencies of homozygotic mother with heterozygotic neonate were 15.9% in both HPA-3a and HPA-15b, 9.1% in HPA-15a, 6.8% in HPA-3b, and 2.3% in both HPA-2a and HPA-6a. In this study, maternal HPA antibodies were found in five samples, whereas HLA class I antibodies were found in seven maternal plasma samples from the antibody screen. The results from this study have demonstrated that HPA mismatch is not the main cause for the production of HPA alloantibodies.

This study was conducted in order to assess the safety and tolerability of Agaricus blazei Murrill (ABM) in general toxicological studies by Ames tests in vitro and in 28-day feeding toxicity experiments. There were no dose-dependent increases or decreases in the number of revertant colonies both with and without metabolic activation in Ames tests. Doses of 10, 5 and 0.1 mg/per mouse of ABM daily were administered by oral gavage to mice (n=10) for 28 days. The effects on clinical observations, clinical pathology, and histopathology were evaluated. There were no significant changes in the brain, heart, kidney, liver, spleen, adrenal gland, testes or ovaries visually. With increasing doses, male and female treated mice did not show any gradual elevation of serum concentration in any of the nine items we examined, except for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in females. The AST levels of the treatment by medium or high dose and the ALT levels of the treatment by high dose in females were abnormal in comparison to those of the baseline control group, with significant differences. On studying the histological changes in mice, tissue sections of negative control and experimental groups exhibited no apparent pathological alterations. In summary, the Ames test, pathology determinations, biochemical analysis and routine blood parameters were all normal, except for AST and ALT in females. Results showed that the statistical differences observed in one sex were not observed in the other and were not dose dependent.

This study was conducted to evaluate the hepatoprotective effect of Agaricus blazei Murrill extract (ABM) against experimentally induced carbon tetrachloride (CCl(4)) toxicity in male BALB/c mice. The experiments included a normal group (no induction by CCl(4)), CCl(4-)induction group (with hepatotoxicity by CCl(4) and without treatment) and experimental groups with low dose (200 mg) or high dose (2,000 mg) of ABM extract (per kilogram mouse weight). All groups other than the normal group were treated with intraperitoneal injections of CCl(4) twice a week. Mice were tube-fed with experimental ABM extracts or double-distilled water, accordingly, on the remaining four days each week. The whole experimental protocol lasted 8 weeks; blood and liver samples were collected for biochemical and tissue histochemical analysis. Only administration of a high dose of ABM to treatment groups resulted in a significant abrogation of CCL(4)-induced increase of serum aspartate aminotransferase (AST) and alanine transaminase (ALT). Post-treatment with ABM also did not significantly reverse the alterations of glutathione peroxidase (GSHPx) and catalase. Both high- and low-dose ABM treatment reduced hepatic necrosis and fibrosis caused by CCl(4) in comparison with the CCl(4) control group in the histochemical analyses. Our results suggest that the ABM extract affects the levels of ALT and AST in mice.

Objectives To evaluate the association between AGEs and atherosclerotic lipid profiles among aging diabetic patients in Taiwan. Design and Methods After age and gender matching, we selected 207 diabetic subjects and 174 diabetic subjects with proteinuria. Lipid profiles, including total cholesterol (TC), triglycerides (TG), high density cholesterol-lipoprotein (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were measured using standard methods. AGEs were measured with the immunoassay method. Results In general, males were heavier; however, females had higher AGEs, fasting glucose (GLU), TC, HDL-C and LDL-C levels than males, and had higher TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C ratios compared to males. AGEs were more strongly correlated with TG levels and TCL/LDL-C, LDL-C/HDL-C and TG/HDL-C ratios when compared to glucose or hemoglobin A1c. Subjects had higher AGEs levels (≧ 2.0 AU) with more adverse lipid profiles. Conclusion AGEs seem to be a good biomarker to evaluate the association between diabetes and atherosclerotic disorders in aging diabetes.

Antrodia cinnamomea is an expensive and highly valued folk medicinal fungus that grows only inside the rotten trunk of Cinnamomum kanehirae, an evergreen broad-leaved tree. This fungus has recently been used commercially in the formulation of nutraceuticals and functional foods in Taiwan. It has been used for centuries as a detoxificant in cases of food poisoning, diarrhea, vomiting, hepatic disease and various kinds of cancers. The present study investigated the effects of Antrodia cinnamomea on mutagenicity using a bacterial reverse mutation assay employing the Salmonella typhimurium strains TA97, TA98, TA100, TA102, and TA1535. The effects of Antrodia cinnamomea on chromosome structure were tested in Chinese hamster ovary (CHO) cells. Antrodia cinnamomea was not mutagenic in all bacterial strains and it was not genotoxic in CHO cells.

CHU, NAIN-FENG, JIN-BIOU CHANG, AND SHIHMING SHIEH. Plasma leptin, fatty acids, and tumor necrosis factor-receptor and insulin resistance in children. Obes Res. 2003;11:532-540. Objective: To evaluate the effect of plasma leptin, nonsterified fatty acids (NEFAs), and tumor necrosis factor-receptor 1 (TNFR1) on plasma insulin and insulin-resistance status in children. Research Methods and Procedures: One thousand thirtytwo children (521 boys and 511 girls) were included in this study. We measured plasma insulin and leptin levels by radioimmunoassay, plasma NEFA levels by enzymatic acyl-coenzyme A synthase–acyl-coenzyme A oxidase spectrophotometric methods, and TNFR1 levels by enzyme-linked immunosorbent assay. We calculated insulin resistance index (IRI) using homeostasis model assessment and calculated insulin-resistance syndrome summary score (IRS) by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride, high-density lipoprotein-cholesterol (inverse), and insulin levels. Results: Overweight children had higher BP, plasma leptin, and insulin levels and higher IRI and IRS than normalweight children. Plasma leptin and TNFR1 were positively correlated with insulin levels, IRI, and IRS. The correlation coefficients of leptin and TNFR1 in IRI were 0.53 and 0.12, respectively, for boys and 0.25 and 0.18, respectively, for girls. In multivariate regression analyses, TNFR1 was positively associated with insulin level and IRI in girls; NEFA was positively associated only with IRS. Plasma leptin levels were significantly positively associated with insulin levels, IRI, and IRS, even after adjusting for BMI and other potential confounders. Discussion: Overweight children had higher BP, plasma insulin, and leptin levels and adverse insulin-resistance status than normal-weight children. Plasma leptin levels, rather than NEFA and TNFR1, may play a significant role in the development of hyperinsulinemia and insulin resistance in children.