Preservation of red blood cell antigenicity in a new storage solution in vitro.

INTRODUCTION: Red blood cell (RBC) storage solution is used for suspending and preserving RBCs for later use in in vitro immunohematology testing. Proper RBC preservation is crucial for obtaining accurate results in RBC phenotyping and pretransfusion antibody screening tests. Haemolysis or RBC antigen degradation during storage can result in inaccurate RBC phenotyping, thereby decreasing the sensitivity of pretransfusion antibody screening and identification assays. The conventional RBC storage solutions usually contain adenosine, adenine, and antibiotics. We designed an RBC storage solution and determined whether it could preserve RBC integrity for 70 days. MATERIALS AND METHODS: The new storage solution has a different formula from that of the conventional solution-in particular, it is strengthened with polyethylene glycol (PEG). The extent of haemolysis and hemagglutination reactivity of the RBC antigen systems, Rh, Duffy, Kidd, Lewis, MNS, P1, and the rare antigen Mia (which has a low prevalence antigen in most parts of the world but a higher prevalence in Taiwan), in the new RBC storage solution was compared with that of the conventionally preserved RBC storage solution. RESULTS: The RBCs preserved in the new solution for 70 days retained a similar haemolysis grade as those preserved in the control solution for 28 days. Although both solutions largely preserved RBC antigenicity, the decline in RBC hemagglutination scores in new solution often occurred later than that in the control solution in most antigen phenotyping assays, especially labile antigens such as D, P1, and M. CONCLUSION: The new solution reduces haemolysis more effectively and preserves antigenicity throughout the 70-day storage period. Moreover, Mia antigen is more stable in the experimental group.

Hypermethylation of SHISA3 DNA as a blood-based biomarker for colorectal cancer.

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.

The roles of first phase, second phase insulin secretion, insulin resistance, and glucose effectiveness of having prediabetes in nonobese old Chinese women.

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.

Influence of Diabetogenic Factors on Fasting and Postprandial Glucose Levels in Patients with Type 2 Diabetes Mellitus.

Background: This study evaluated the relative influence of insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) in determining the difference between fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (ΔPG), in a Chinese population with type 2 diabetes (T2D) mellitus. Methods: In total, we enrolled 1213 participants with T2D (479 women). IR, FPIS, SPIS, and GE were estimated by using equations we built previously. ΔPG was defined as FPG - PPG. Results: The relative contribution of the four diabetogenic factors (DFs) was analyzed by multiple linear regression, and GE was the greatest contributor in the ΔPG value (ß = 0.171, P < 0.001), whereas IR had the least influence on ΔPG (ß = -0.040, P = 0.439). DFs were analyzed by using binary logistic regression to ascertain if ΔPG ≥0 (high fasting plasma glucose, HFG). Three models were built: Model 0: SPIS, Model 1: SPIS + FPIS, and Model 2: Model 1 + GE. Model 2 had the most accurate predictive power; the equation for Model 2 is P = 1/(1 - e-x), where x = -11.88 + 312.89 × (GE) -1.22 × log(SPIS) +1.63 × log(FPIS). In this equation, P refers to the risk of HFG. Conclusions: For Chinese patients, GE had the most profound effect in determining ΔPG, followed by FPIS, SPIS, and IR. The model suggested that participants with high FPIS, SPIS, and GE would have a high incidence of HFG.

Protective Effect of Hepatitis B Against Metabolic Syndrome in Patients with Nonalcoholic Fatty Liver Disease But Not in Normal Individuals.

Background: Both hepatitis B (HB) and nonalcoholic fatty liver disease (NAFLD) are related to metabolic syndrome (MetS); however, this relationship remains controversial. In this study, we determined the effects of NAFLD and HB infection on the risk of MetS among elderly individuals. Methods: In total, 24,500 individuals aged >65 years were enrolled; they were classified into four groups: normal individuals (N), patients with only HB infection without abnormal echogenicity (HB-alone), patients with only abnormal echogenicity or fatty liver alone (FL-alone), and patients with both HB infection and abnormal echogenicity (HB-FL). Results: After adjustment for age, compared with group N, men and women with NAFLD (FL-alone and HB-FL) had a significantly higher risk of MetS, whereas no significant difference was observed in the incidence of MetS between groups HB-alone and N. However, group HB-FL had a lower risk of MetS than did group FL-alone. HB infection (HB-alone and HB-FL) was associated with a lower risk of high triglycerides (TGs) and fasting plasma glucose (FPG) than HB infection absence (groups N and FL-alone) in men and women. Lower risk of TG derangement was observed in group HB-alone than in group N. In addition, both men and women in group HB-FL had a lower risk of TG and FPG abnormalities than in group FL-alone, whereas a decrease in incidence of high waist circumference and blood pressure was observed only in men. Conclusion: HB infection protects against MetS development, only in patients with HB infection and NAFLD, but not in normal individuals. Additional studies are warranted to clarify the pathogenesis.

Correction: Effect of body mass index on diabetogenesis factors at a fixed fasting plasma glucose level.

[This corrects the article DOI: 10.1371/journal.pone.0189115.].

Effect of body mass index on diabetogenesis factors at a fixed fasting plasma glucose level.

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.

Relationship between plasma adropin levels and body composition and lipid characteristics amongst young adolescents in Taiwan.

Adropin is a 76 amino acid peptide hormone with a molecular weight of 4999.9Da that may be associated with energy homeostasis, insulin resistance and lipid metabolism in mice and human. There is only a few studies that examine plasma adropin levels and body composition in children. This study is to evaluate the relationship between plasma adropin levels, body composition and lipid variables amongst young adolescents in Taiwan. We examined 492 adolescents (269 females and 223 males) ranging from 12 to 15 years old, with a mean age of 13.6 years. Body composition was measured using impedance method by Tanita-BC418. Plasma lipid variables were measured using standard methods and plasma adropin levels were measured using the ELISA method. There was no significant difference in plasma adropin levels between males and females (3.52 vs. 3.58ng/ml). Plasma adropin levels were negatively correlated with fat free mass (r=-0.12, p<0.01). More interestingly, children with higher plasma adropin levels had lower waist-to-hip ratios (WHR) and lower body fat percentage by mass. Furthermore, there is no difference in lipid profiles in high vs. low adropin subjects. Plasma adropin levels are not consistency associated with body composition and no association with lipid variables amongst Taiwanese adolescents. The role of adropin in the development of obesity is still not clear, and further studies are need especially for children.

Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells.

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.

High normotension is associated with future metabolic syndrome but not cardiovascular disease: A 10-year longitudinal study.

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 investigate the relationships among normal-range BP, metabolic syndrome (MetS), and CVD.A total of 9133 nonmedicated normotensive participants, 4634 males and 4499 females, aged 60 years or older were enrolled in a standard health examination program at 2 academic hospitals and a health screening center in Taiwan. The study subjects were divided into 3 groups according to their BP. The systolic BP (SBP) ranges of groups 1, 2, and 3 were 91 to 100, 101 to 110, and 111 to 119 mmHg, whereas the diastolic BP (DBP) ranges of groups 1, 2, and 3 were 51 to 60, 61 to 70, and 71 to 79 mmHg, respectively.In the SBP3 group, both sexes had a higher odds ratio (OR) for having MetS or abnormal MetS components, except for triglycerides. Females in the DBP3 group had a higher OR for having MetS at baseline. After the follow-up period, the SBP3 group had a significantly higher hazard ratio (HR) for developing MetS. Males in the DBP3 group and females in the DBP2 and DBP3 groups had a significantly higher HR for developing MetS. Neither the SBP3 group nor the DBP3 group had a higher HR for developing nonfatal CVD. In the Kaplan-Meier analysis, SBP and DBP in both sexes showed statistical significance as predictors of MetS, but not of nonfatal CVD.High normotensive elderly individuals have an elevated risk of developing MetS at baseline and within 10 years of follow-up, but they are not at increased risk of CVD. Preventive interventions, such as life-style modification, should be offered early even to the apparently healthy elderly.

Identification of Normal Blood Pressure in Different Age Group.

The concept of using single criterion of normal blood pressure with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg for all ages is still disputable. The aim of the study is to identify the cutoff value of normotension in different age and sex groups.Totally, 127,922 (63,724 men and 64,198 women) were enrolled for the analysis. Finally, four fifths of them were randomly selected as the study group and the other one fifths as the validation group. Due the tight relationship with comorbidities from cardiovascular disease (CVD), metabolic syndrome (MetS) was used as a surrogate to replace the actual cardiovascular outcomes in the younger subjects.For SBP, MetS predicted by our equation had a sensitivity of 55% and specificity of 67% in males and 65%, 83% in females, respectively. At the same time, they are 61%, 73% in males and 73%, 86% in females for DBP, respectively. These sensitivity, specificity, odds ratio, and area under the receiver operating characteristic curve from our equations are all better than those derived from the criteria of 140/90 or 130/85 mmHg in both genders.By using the presence of MetS as the surrogate of CVD, the regression equations between SBP, DBP, and age were built in both genders. These new criteria are proved to have better sensitivity and specificity for MetS than either 140/90 or 130/85 mmHg. These simple equations should be used in clinical settings for early prevention of CVD.

Association of complete blood cell counts with metabolic syndrome in an elderly population.

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 < 74 years old), old old (OO: ≥ 75 and < 84 years old), and oldest old (ODO: ≥ 85 years old). The MetS components were determined, and correlations between MetS and hematogram components were evaluated using Pearson and multivariate linear regression analyses. The hematogram components were the independent variables evaluated separately against the dependent variable (MetS components). RESULTS: While SBP and HDL-C increased, most other MetS and hematogram parameters decreased in men with age. Fewer significant differences were noted among the women. In the YO and OO groups for both genders, the subjects with MetS had higher WBC and Hb. None of the hematogram components were different for subjects with or without MetS in the ODO group. Multiple regression results show that most of the relationships between hematogram and MetS components disappeared in the ODO groups. The WBC levels were mainly correlated with WC and TG. At the same time, Hb was associated with BP, FPG, and LDL-C. Compared to WBC and Hb, PLT was least related to MetS, except in the cases of LDL-C and TG. Among the MetS components, BMI, LDL-C, and TG were consistently related to all the hematogram components in YO and OO men. However, only TG had the same consistency among YO and OO women. CONCLUSIONS: This study's three major findings are as follows: WBC and Hb are associated with MetS, even among the YO and OO groups, regardless of gender; among the three hematogram components, Hb had the strongest and PLT had the weakest correlation with MetS; and TG is not the only component with relatively higher r values, and it is related to all hematogram components.

The relationships between hematogram and metabolic syndrome in elderly subgroups: A Taiwan cohort study.

BACKGROUND: Abnormal hematogram components could predict future metabolic syndrome (MetS) and diabetes. However, there was no study focusing on the subgroups of the elderly. In this ten-year longitudinal study, we investigated the association between hematogram components, future MetS and diabetes in the elderly. METHODS: Subjects above 65 years were divided into three groups by age (young old: ≧65 and <75, old-old: ≧75 and <85 and oldest-old ≧85).By using multiple logistic regression, the hazard ratio (HR) of higher hemoglobin (Hb), white blood cell count (WBCC) and platelet (PLT) to have future MetS and diabetes were evaluated. RESULTS: There were 15169 subjects in the young-old group, 3536 in the old-old group and 202 in the oldest-old group, respectively. After 10 years follow-up, only higher WBCC and Hb levels (>5.0×10(3), 15 g/dL, respectively) was correlated to future MetS in young-old men (adjusted HR: 1.242, 1.166, respectively). In addition, higher Hb (>13.7 g/dL) was originally associated with future MetS in young-old and old-old women but failed in adjusted HR. Moreover, the PLT did not correlate with any of the endpoints. Finally, higher chances of diabetes could be noted with higher WBCC in both men and women (adjusted HR: 1.404, 1.206, respectively). CONCLUSIONS: The associations between hematogram and future MetS were different in each subgroup of the elderly. Higher WBCC and Hb levels could predict future MetS in young-old men. Moreover, Higher WBCC is positively correlated with future diabetes in both young-old men and women.

BMI, body fat mass and plasma leptin level in relation to cardiovascular diseases risk factors among adolescents in Taitung.

BACKGROUND: To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan. METHODS: A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender-specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age. RESULTS: After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL-cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL-cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r=0.59, p<0.01). CONCLUSIONS: BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents.

Folate deficiency-triggered redox pathways confer drug resistance in hepatocellular carcinoma.

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.

Using white blood cell counts to predict metabolic syndrome in the elderly: A combined cross-sectional and longitudinal study.

BACKGROUND: Metabolic syndrome (MetS) has an important implication from a preventive medicine perspective as early recognition and intervention will reduce associated mortality and morbidity. To better identify patients at risk for developing MetS and cardiovascular disease, we conduct a combined cross-sectional and longitudinal study to shed light on the elevated white blood cell (WBC) level in elderly. METHODS: A total of 10,463 subjects were eligible for analysis. In the first stage of study, subjects were enrolled in the cross-sectional study to find out not only the correlation between WBC and MetS but also the optimal cut-off value of WBC with higher chances to have MetS. In the second stage of current study, subjects with MetS at baseline were excluded from the same study group, and performed a median 6.8-year longitudinal study to validate the optimal cut-off value of WBC predicting MetS. RESULTS: WBC is significantly higher in the group with than without MetS in both genders. All MetS components were associated with WBC in multivariate analysis except diastolic blood pressure and fasting plasma glucose. In the longitudinal study, WBC showed to be a good predictor of MetS in both genders. CONCLUSION: WBC is a good marker to identify the high risk subjects having MetS in the current status or in the future. Elderly with a higher WBC and without any underlying chronic diseases should receive more attention on the potential to develop MetS.

Chitosan oligosaccharides in combination with Agaricus blazei Murill extract reduces hepatoma formation in mice with severe combined immunodeficiency.

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 tumor­bearing 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.

Mean arterial pressure is better at predicting future metabolic syndrome in the normotensive elderly: a prospective cohort study in Taiwan.

OBJECTIVE: To compare four different blood pressure (BP) measurements-systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)-in predicting future metabolic syndrome (MetS) among the normotensive elderly population, and to estimate the optimal cutoff value of the best single measurement for clinical practice. METHODS: A total of 2782 non-medicated participants aged ≥ 60 years were enrolled in a standard health examination program in Taiwan from January 2004 to December 2013. Two thirds of the participants were randomly designated as the training group (n=1855) and the other one third as the validation group (n=927). The mean follow-up time was 3.60 years for both the training and validation groups. MAP and PP were calculated from SBP and DBP. RESULTS: SBP, DBP, and MAP were associated with future MetS, whereas PP was not. MAP had the largest hazard ratio in Cox regression (men 1.342 [95% CI 1.158-1.555] and women 1.348 [95% CI 1.185-1.534] in the training group; men 1.640 [95% CI 1.317-2.041] and women 1.485 [95% CI 1.230-1.794] in the validation group) and the largest area under the receiver operating characteristic curve (men 0.598 ± 0.021 and women 0.602 ± 0.021 in the training group). Multivariable Cox regression further indicated that a higher MAP level was independently associated with the future occurrence of MetS. Participants with MAP above the cutoff value (84.0mm Hg for men, 83.3mm Hg for women) had a higher cumulative incidence of MetS than did their counterparts after four years' follow-up in both the training and validation groups. The results derived from the training data could be replicated in the validation data, indicating that the results were generalizable across distinct samples. CONCLUSIONS: MAP is more accurate than SBP, DBP, and PP in predicting future MetS among the normotensive geriatric population. Calculation of MAP is recommended when dealing with normotensive patients aged ≥ 60 years in clinical practice.

Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1 cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9-signaling pathways.

Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors.