MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer.

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as MSP58) is a protein originally identified in the nucleus and cytoplasm that is involved in the cell cycle. High expression of MCRS1 increases tumor growth, invasiveness, and metastasis. The mechanistic relationships between MCSR1 and proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT) remain to be elucidated. We clarified these relationships using immunostaining of tumor tissues and normal tissues from patients with gastric cancer. High MCRS1 expression in gastric cancer positively correlated with Ki-67, Caspase3, CD31, Fibronectin, pAKT, and pAMPK. The hazard ratio of high MCRS1 expression was 2.44 times that of low MCRS1 expression, negatively impacting patient survival.

Comprehensive analysis in mucin-producing urothelial-type adenocarcinoma of the prostate: case study with literature review.

It is critical to distinguish the rare neoplasm of mucin-producing urothelial-type adenocarcinoma of the prostate (MPUAP) from either prostate origin or metastatic adenocarcinoma. This is mainly because they have different tumor staging, clinical behavior and treatment plans. In the current study, we try to fulfill the lack of knowledge in this field. There were totally 24 MPUAP cases including previous reported 23 cases and adding one new MPUAP case in the current study. We performed IHC and 78 genes panel analysis in two cases of ours. Most of the cases had urinary obstruction symptoms and normal PSA level. Pathological features showed dissection of the stroma by mucin pools and glands lined by pseudostratified columnar mucinous epithelium with varying degrees of cytological atypia. The IHC results showed positive for CK20, CEA, CDX-2, ß-catenin, p53, MUC2 and MUC5AC, negative for PSA, AMACR, GATA3, MUC6, AR and NKX3.1 and variable expression for HMWCK and CK7. Genetic analysis revealed concurrent mutations of FAT1 (c.10001 T>C) and HNF1A in both cases. The similar morphology features of MPUAP and colorectal adenocarcinoma were seen. Membranous staining pattern of ß-catenin and genetic mutation of FAT1 and HNF1A are two distinct features in MPUAP.

The relationships between hemoglobin and insulin resistance, glucose effectiveness, and first- and second-phase insulin secretion in adult Chinese

ABSTRACT Objective We denote the four major factors related to the development of type 2 diabetes (T2D) as "diabetes factor" (DF); increased insulin resistance (IR); decreased glucose effectiveness (GE); and the first-and-second-phase of insulin secretion (FPIS, SPIS). The level of hemoglobin (Hb) was found to be related to IR and FPIS, but no-known studies focused on its role in relation to SPIS and GE. In this study, we aim to evaluate the relationships between Hb and all four DFs in the same individual. Subjects and methods We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured according to equations published in our previous studies. To compare the slopes between Hb and the four DFs with different units, we converted their units to percent of change per unit of increased Hb. Results Age, HDL-cholesterol and GE were higher in women; BMI, blood pressure, LDL-cholesterol, TG, Hb, FPIS, SPIS and IR were higher in men. After they were converted into percentage, the closeness of their relationships to Hb, from the highest to the lowest, were GE, IR, FPIS and SPIS for women and IR, GE, FPIS and SPIS for men. GE was the only one negatively related to Hb. Conclusions Our data showed that IR, FPIS and SPIS were both positively and, GE negatively, related to the Hb in adult Chinese. For women, GE had the closest association with Hb; for men, it was IR. Both phases of insulin secretion had relatively weaker relationships than IR and GE.

Surface-modified nanocrystalline cellulose from oil palm empty fruit bunch for effective binding of curcumin.

Rod-shape particles have been a good drug carrier due to the long circulatory time, tumor accumulation and high cellular uptake in body. Acid-hydrolysed nanocrystalline cellulose (NCC) from empty fruit bunch exhibited a width of 13-30nm and a length of 150-360nm in rod-shape structure. NCC holds good potential as a bio-based drug carrier owing to its biodegradability and biocompatibility. Fourier-transform infrared spectroscopy results confirmed the binding of curcumin onto the NCC modified with tannic acid (TA) and decylamine (DA). TA-DA modification rendered NCC with a higher level of hydrophobicity, as evidenced by a substantial increase in contact angle from 45° to 73°. The modified NCC had the curcumin-binding efficiency in the range of 95-99%, which is at least twofold higher than the unmodified NCC at any curcumin concentration tested. This remarkable curcumin-binding effciency was comparable to that of commercialized NCC from wood-based origin. This work suggests NCC as a superior and sustainable drug carrier, while TA-DA modification is a promising approach to alter the surface property of NCC for an efficient binding of curcumin.

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.

CIP2A is a poor prognostic factor and can be a diagnostic marker in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma. CIP2A has recently been described as a prognostic marker in many cancers. In this study, we assessed the value of this novel prognostic marker in PTC. A total of 178 surgical specimens of both benign and malignant thyroid tumors were collected. Immunohistochemical staining for CIP2A, HBME-1, galectin-3, and CK19 was performed. Western blotting for CIP2A was also performed. CIP2A was expressed in 85.3% of malignant tumors and 12.1% of benign tumors. ROC analysis showed that the AUC for CIP2A was higher than those for other tumor markers. Western blotting showed that CIP2A expression was higher in PTC than in other tumors. Poor progression-free survival was observed in the high-CIP2A expression group. High CIP2A expression is a poor prognostic factor and can be a diagnostic marker in PTC. The presence of any two of the three indicated makers (CIP2A, galectin-3, and HBME-1) is strongly correlated with the diagnosis of PTC.

Effects and Factors Related to Adherence to A Diabetes Pay-for-Performance Program: Analyses of a National Health Insurance Claims Database.

OBJECTIVES: To compare the effects of a diabetes pay-for-performance (P4P) program on diabetes-related/nondiabetes-related healthcare utilization/expenses between participants who adhered to the program and those who did not, and explore factors related to program adherence. DESIGN: A secondary data analysis with a natural experimental design. SETTING: Taiwan's National Health Insurance claims database (2001-2011) of newly diagnosed patients with diabetes in 2001 was used for the analyses. PARTICIPANTS: The database under analyses contained 119,970 patients who were newly diagnosed with diabetes in 2001. Longitudinal data from 2001 to 2011 were obtained. A sample of 5592 patients who were enrolled in the diabetes P4P program during 2003-2006 was identified. After a 3-year follow-up of the enrolled patients, 2647 (47.3%) of them adhered to the program. To minimize the differences between the characteristics of the patients who adhered to the program and those who did not, propensity score matching was adopted. A total of 5294 patients (adherence: 2647 vs nonadherence: 2647) were included for analyses. MEASUREMENTS: We estimated utilization/expenses of healthcare services for both groups at 6 time points and applied t tests to test each utilization and expense of healthcare services between the 2 groups. A repeated-measures analysis of variance was applied to examine changes in the annual diabetes-related healthcare service expenses and total annual expenses by group. Logistic regression models were used to examine factors related to program adherence. Covariates included participant age, gender, diabetes-related complications, Charlson Comorbidity Index, Continuity of Care Index, time since diagnosis of diabetes, hospitalization in the previous year, and location receiving healthcare services. RESULTS: Total annual healthcare expenses spent by the adherence group were significantly lower than those of the nonadherence group. Gender, continuity of care, time since diagnosis of diabetes, hospitalizations in the previous year, and location receiving healthcare services were factors related to program adherence. CONCLUSIONS: Long-term, beneficial effects of the diabetes P4P program might have been present if patients had adhered to the program. Interventions and strategies which could improve program adherence and continuity of care are suggested to achieve optimal disease control and clinical outcomes.

Urokinase plasminogen activator receptor and its soluble form in common biopsy-proven kidney diseases and in staging of diabetic nephropathy.

OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR), derived from membrane bound uPAR, is associated with inflammatory diseases. In the present study, we explored the expression of uPAR/suPAR in common biopsy-proven kidney diseases and the relationship between suPAR and staging of type 2 diabetic nephropathy (DN). DESIGN AND METHODS: Serum samples for suPAR and renal tissues for uPAR staining were investigated in various common kidney diseases. The levels of serum suPAR were measured and adequate cut-off values of different stage of DN were calculated by receiver operating characteristic (ROC) curve. RESULTS: In our results, the expression of uPAR on renal tissues was pronounced in the majority of kidney diseases. Comparing of expression of uPAR among different kidney diseases, it was strongest in minimal change disease (MCD) and weakest in chronic interstitial nephritis. Serum suPAR in most kidney diseases, except of MCD, was significantly elevated and was highest in DN. As for DN and suPAR, we found that suPAR progressively increased with staging of DN. Moreover, suPAR was linearly and negatively related to estimated glomerular filtration rate and positively related to the amount of proteinuria. By ROC curve, the cut-off values of suPAR in DN for assessing development increased with the progression of the disease. CONCLUSIONS: We concluded that uPAR/suPAR is elevated in most kidney diseases and that suPAR is a useful biomarker for assessing stages of DN.

Chaperonin-containing t-complex protein-1 subunit ß as a possible biomarker for the phase of glomerular hyperfiltration of diabetic nephropathy.

In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit ß (TCP-1ß) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1ß and type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (C cr), and kidney tissues were harvested for evaluation of TCP-1ß expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1ß. Results showed that C cr and the expression of TCP-1ß in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1ß was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1ß level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1ß is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

The neuroprotective role of metformin in advanced glycation end product treated human neural stem cells is AMPK-dependent.

Diabetic neuronal damage results from hyperglycemia followed by increased formation of advanced glycosylation end products (AGEs), which leads to neurodegeneration, although the molecular mechanisms are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). AMPK is a critical evolutionarily conserved enzyme expressed in the liver, skeletal muscle and brain, and promotes cellular energy homeostasis and biogenesis by regulating several metabolic processes. While the mechanisms of AMPK as a metabolic regulator are well established, the neuronal role for AMPK is still unknown. In the present study, human neural stem cells (hNSCs) exposed to AGEs had significantly reduced cell viability, which correlated with decreased AMPK and mitochondria associated gene/protein (PGC1α, NRF-1 and Tfam) expressions, as well as increased activation of caspase 3 and 9 activities. Metformin prevented AGEs induced cytochrome c release from mitochondria into cytosol in the hNSCs. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. Metformin also significantly rescued hNSCs from AGE-mediated mitochondrial deficiency (lower ATP, D-loop level, mitochondrial mass, maximal respiratory function, COX activity, and mitochondrial membrane potential). Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARγ, Bcl-2 and CREB). These findings extend our understanding of the molecular mechanisms of both AGE-induced neuronal toxicity, and AMPK-dependent neuroprotection by metformin. This study further suggests that AMPK may be a potential therapeutic target for treating diabetic neurodegeneration.

VEGF-D as a marker in the aid of malignant metastatic pleural effusion diagnosis.

BACKGROUND: The sensitivity in cytology diagnosis of malignant metastatic pleural effusion (MMPE) is insufficient nowadays due to the similarity of the reactive mesothelial cells and malignant cells. Vascular endothelial growth factor (VEGF) is one of the key factors in tumor lymphangiogenesis and metastasis. Therefore, the aim of this study was to evaluate the value of VEGF and its homologs in the aid of MMPE diagnosis. METHODS: A total of 217 pleural effusions samples were eligible for analysis. Among them, 81 malignant and 22 benign cases were made into the cell blocks for the immunocytochemical (ICC) staining of VEGF-A, VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3 expression. Another 114 samples (41 malignant and 73 benign cases) were subjected to the ELISA test for the protein level of VEGF-D. RESULTS: In a total of 156 MMPE, only VEGF-D expression by ICC stain was significantly different between malignant (92.6%) and benign cases (9.1%) with P<0.001 in either nuclear or cytoplasmic staining. Only 6 malignant cases showed negative stain results. In addition, 3 of the 4 lung small cell carcinoma were immunoreactive for VEGF-D. However, some lymphocytes also showed nuclear staining pattern of VEGF-D. In contrast, the ELISA test for the VEGF-D protein levels failed to demonstrate the difference between malignant and benign pleural effusions. CONCLUSIONS: Among VEGF homologs, MMPE from various kinds of tumor origin, VEGF-D showed 92.6% rate of positive expression. ICC stain of VEGF-D is a useful marker in the aid of MMPE diagnosis.

Platelet count can predict metabolic syndrome in older women.

Platelet count (PC) has been found to be related to the metabolic syndrome (MetS). However, the role of PC on MetS remained unclear. In order to evaluate the relationship between PC and MetS components cross-sectionally and determine the optimal cutoff PCs for predicting the subsequent risk of MetS development with sex specificity, two stages included cross-sectional (stage 1) and prospective (stage 2) cohort study were conducted. Stage 1 involved 10 579 subjects aged ≥60 years, of which 7718 subjects advanced to stage 2 with a mean 3.8 year follow-up were enrolled. The MetS components and PC were determined. The PC cutoffs for higher chances of developing MetS in stage 1 were calculated using receiver operating characteristic (ROC) curve analyses. In stage 2, non-MetS subjects were classified into high-PC (HPC) and low-PC (LPC) groups according to the cutoff values from stage 1. We examined the difference of future MetS incidence and calculated the odds ratio (OR) between these two groups. In stage 1, multiple regression showed that age and triglyceride (both sexes) and waist circumstance and high-density lipoprotein cholesterol (only women) were independently correlated with PC. There was significant difference in the area under the ROC curve (AUC) only of HPC women, which exceeded the standard curve (AUC = 0.542, p < 0.001), with a cutoff PC of 223 × 10(3)/µl. HPC women had an OR of 1.287 (95% confidence interval: 1.135-1.461) of developing MetS after 3.8 years. The Kaplan-Meier curve demonstrated a higher incidence of MetS development in HPC women. In conclusion, our results suggest that PC was associated with MetS with sex effects. Most of the MetS components were independent factors for increasing PC, and the risk for subsequent development of MetS was noted when PC >223 × 10(3)/µl in elderly women.

The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes.

OBJECTIVE: Impaired insulin sensitivity (SI) and ß-cell function are the two main causes of type 2 diabetes (T2D) and are related to low-grade inflammation status. Trivalent chromium has shown to improve SI in our previous study. This might be due to the ability of decreasing interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) shown in animal studies. In the current study, we measured SI, ß-cell function, and plasma levels of IL-6 and TNF-α after treatment of chromium chloride (GaCr) in T2D. RESEARCH DESIGN AND METHODS: Sixty-six patients were randomly assigned to the 20 g of GaCr milk powder studying group or the milk powder placebo group. Oral glucose tolerance test was performed before and after the treatment. The SI and the ß-cell function were measured as well. RESULTS: The SI was significantly improved. At the same time, the static insulin responsivity index (Φs) was significantly higher after the treatment (p = 0.003). On the other hand, the dynamic insulin responsivity index (Φd) remained unchanged. Interestingly, a significant decrease in the IL-6 level after the treatment (p = 0.015) was noted. Although there was a trend of decreasing in TNF-α, it was not statistically significant. Finally, there was no significant correlation between the δ-IL-6, SI, and Φd after GaCr treatment. CONCLUSIONS: In conclusion, other than the improvement of SI, GaCr could also improve the second phase of insulin responsivity (Φs) and IL-6. However, δ-IL-6 was correlated with neither δ-SI nor δ-Φs which indicated that the improvement of SI and Φs might involve mechanisms other than lower inflammatory effect.

The adipokines and inflammatory marker in young type 2 diabetics with metabolic syndrome: A pilot study.

OBJECTIVE: The purpose of the metabolic syndrome (MetS) concept was to early identify subjects having risk for developing cardiovascular diseases and diabetes, which of both are involved in low grade inflammation and obesity. We wish to explore the role of adipokines and inflammatory marker in young type 2 diabetics (YDM) with MetS. METHODS: Forty-eight YDM patients were divided to 2 and 3 groups according to the presence of the MetS (MetS+ and MetS-), and the numbers of MetS component (MetS-2 to MetS-4 with 1-2, 3, and 4-5 components) respectively. Plasma adipokines (tumor necrosis factor-α; TNF-α and adiponectin) and C-reactive protein (CRP) were measured and compared among groups. RESULTS: Blood pressure (BP), body mass index (BMI), and plasma triglyceride (TG) levels were higher in the group with MetS+ than that of MetS-. Except for diastolic BP, BMI, waist, and plasma TG levels, which were generally lower in the MetS-2 group, the rest demographic characteristics were not different among these three groups. Finally, the plasma adiponectin, CRP and TNF-αlevels were not different between both groups with or without MetS; and also among these three groups regardless the component numbers they had. CONCLUSION: YDM with MetS might have non-significant lower adiponectin and higher CRP levels compared to subjects without MetS. It needs prospective study with larger scale to explicit the role of cytokines and inflammatory markers in YDM with MetS.

Variability in hemoglobin A1c predicts all-cause mortality in patients with type 2 diabetes.

BACKGROUND: To evaluate the relationship between hemoglobin A1c variability and all-cause mortality in type 2 diabetic patients. METHODS: This was a retrospective cohort study in type 2 diabetic patients followed for at least 2 years between 2003 and 2009. A1C variability was determined from the standard deviation or coefficient of variation of serial A1C values (A1C(SD) or A1C(CV)). Subjects were categorized into either the high or low A1C variability group according to their A1C(CV) median. Hazard ratios (HRs) of various factors for all-cause mortality were determined from Cox's proportional hazard models. RESULTS: A total of 881 subjects (422 men, 459 women) were included and 73 (8.3%) died during follow-up. The follow-up period was 4.7 ± 2.3 years. All-cause mortality was higher in subjects with high A1C(CV) (11.0% vs. 5.4%, p=0.002). In the Kaplan-Meier failure curve, subjects with higher A1C(CV) demonstrated a trend of higher mortality (p=0.1). In multivariate Cox's proportional hazards models, A1C(SD) and A1C(CV) significantly predicted all-cause mortality with an HR of 1.987 (p=0.02) and 1.062 (p=0.013), respectively, after adjusting for age, gender, body mass index, duration of diabetes, mean systolic blood pressure, use of antihypertensives and statins, mean LDL-cholesterol, smoking status, chronic kidney disease, and mean A1C values (A1C(MEAN)). The ability of A1C(SD) and A1C(CV) to predict all-cause mortality was more evident in subjects with relatively low A1C(MEAN.) CONCLUSIONS: A1C variability is an important risk factor for all-cause mortality in type 2 diabetic patients.

Circulating pro-inflammatory cytokines and adiponectin in young men with type 2 diabetes.

This study was designed to investigate plasma circulating pro-inflammatory cytokines, adiponectin and high-sensitive C-reactive protein (hsCRP) in young men with type 2 diabetes. New-onset young men with type 2 diabetes (young diabetes, YDM; age between 10 and 25) were recruited and divided into a non-obese group (NOYDM, body mass index, BMI ≦ 25 kg/m(2), N = 23) and an obese group (OBYDM, BMI ≧ 25 kg/m(2), N = 24). Twenty-four non-obese non-diabetic young men served as controls. Hemoglobin A1c, fasting glycemic index, lipids, adiponectin, hsCRP, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined. Insulin sensitivity and ß-cell function were calculated using the homeostasis model assessment method (HOMA-IR and HOMA-ß, respectively). Compared to controls, significantly greater HOMA-IR (7.9 ± 1.9 and 10.4 ± 2.5 vs. 1.5 ± 0.3, P < 0.001) and fasting insulin (103.3 ± 21.1 and 209.9 ± 24.4 vs. 48.5 ± 6.7 pmol/l, P < 0.01 and P < 0.001, respectively) were observed in NOYDM and OBYDM. There were significantly lower plasma adiponectin and higher hsCRP and TNF-α levels in OBYDM, whereas higher TNF-α and IL-6 were shown in NOYDM. Spearman rank correlation analysis demonstrated significant correlations between BMI and adiponectin (R = -0.44, P < 0.005), CRP (R = 0.28, P < 0.05), TNF-α (R = 0.42, P < 0.005) and IL-6 (R = 0.33, P < 0.01) in all YDM. Among measured cytokines, only adiponectin was significantly correlated with HOMA-IR, this correlation was abolished when adjusted for age and BMI (R = -0.24, P = 0.12). YDM not only exhibits insulin resistance, but also has inflammatory and atherogenic properties. BMI might be a major determinant of those markers.

Baseline forced expiratory volume in the first second as an independent predictor of development of the metabolic syndrome.

A growing body of evidence strongly supports associations between reduced lung function and insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The present study was undertaken to explore the possibility that reduced lung function is an independent predictor of development of the metabolic syndrome (MetS) and to investigate potential links between reduced lung function and the MetS. A prospective cohort study of reduced lung function as a predictor of subsequent MetS was conducted using 2-year follow-up data for 450 middle-aged adults lacking the MetS at baseline. Data were obtained from the Taipei MJ Health Screening Centers in Taiwan. The MetS was defined according to the modified Adult Treatment Panel III criteria. Over 2 years of follow-up, 26 of the 450 subjects (5.78%) without the MetS at baseline subsequently developed the syndrome. In multiple logistic regression analysis with adjustments for age, sex, body mass index, cigarette smoking, alcohol consumption, and physical activities, reduced forced expiratory volume in the first second (FEV(1)) at baseline remained a predictor of subsequent MetS (relative risk of 4.644, P = .036 for the third [<2.31 L] vs first [>2.88 L] tertile). In Pearson and partial correlation analyses, white blood cell counts and C-reactive protein concentrations were both found to be significantly and negatively correlated with FEV(1). Lower FEV(1) is concluded to serve as an independent predictor of the MetS. Low-grade systemic inflammation is the possible link between reduced lung function and the MetS.

Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes.

Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.

Insulin sensitivity, proinflammatory markers and adiponectin in young males with different subtypes of depressive disorder.

OBJECTIVE: This study was designed to evaluate insulin sensitivity, proinflammatory markers and adiponectin concentration in young males with different subtypes of depressive disorder. METHODS: Nonobese young males with depressive disorder (ages between 18 years and 30 years; body mass index, BMI < or = 25 kg/m(2)) were recruited and divided into reactive depression (RD, N = 14), major depression (MD, N = 21) and bipolar depression (BD, N = 15) based on clinical course and symptom changes in Hamilton rating scale for depression (HAM-D). Fourteen age- and BMI-matched healthy males were enrolled as controls. All of the participants received a 75-g oral glucose tolerance test (OGTT). Insulin sensitivity and beta-cell function were calculated by minimal model method from the frequently sampled intravenous glucose tolerance test. Plasma C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined. RESULTS: Compared to the controls, insulin sensitivity (S(I)) were significantly lower in MD and BD (0.78 +/- 0.09 min(-1)/pmol and 0.75 +/- 0.09 min(-1)/pmol vs. 1.09 +/- 0.08 x 10(-5) min(-1)/pmol, P < 0.05, respectively). Acute insulin response (AIR) to intravenous glucose was elevated in BD as compared to control and RD groups (6079.9 +/- 841.8 pmol vs. 3339.8 +/- 356.4 pmol and 3494.8 +/- 337.7 pmol, P < 0.05, respectively). Plasma adiponectin level was diminished in BD group as compared to the control and RD groups (7.41 +/- 0.45 microg/ml vs. 9.07 +/- 0.54 microg/ml and 9.38 +/- 0.46 microg/ml; P < 0.05 and P < 0.01, respectively). By regression analysis, a significantly negative correlation between HAM-D score and S(I) was found in MD (r = -0.60, P = 0.005) and BD groups (r = -0.57, P = 0.04). CONCLUSIONS: The results suggest that there is an inverse relationship between both major and bipolar depression and insulin resistance in nonobese young males.

Analysis of epistasis for diabetic nephropathy among type 2 diabetic patients.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes, accounting for the majority of patients with end-stage renal disease. The molecular pathogenesis of DN involves multiple pathways in a complex, partially resolved manner. The paper presents an exploratory epistatic study for DN. Association analysis were performed on 231 SNP loci in a cohort of 264 type 2 diabetes patients, followed by the epistasis analysis using the multifactor dimensionality reduction and the genetic algorithm with Boolean algebra. A two-locus epistatic effect of EGFR and RXRG was identified, with a cross-validation consistency of 91.7%.