Shih-Yi Lin

Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population

Background and Aims:  Metabolic syndrome (MS) consists of a cluster of diseases, including obesity, dyslipidemia, hyperglycemia and high blood pressure. The purpose of the present study was to assess the association of MS with adenomas of the rectosigmoid colon, a well‐established precancerous lesion.

Glial activation involvement in neuronal death by Japanese encephalitis virus infection.

Japanese encephalitis is characterized by profound neuronal destruction/dysfunction and concomitant microgliosis/astrogliosis. Although substantial activation of glia is observed in Japanese encephalitis virus (JEV)-induced Japanese encephalitis, the inflammatory responses and consequences of astrocytes and microglial activation after JEV infection are not fully understood. In this study, infection of cultured neurons/glia with JEV caused neuronal death and glial activation, as evidenced by morphological transformation, increased cell proliferation and elevated tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and RANTES (regulated upon activation, normal T-cell expressed and secreted) production. Replication-competent JEV caused all glial responses and neurotoxicity. However, replication-incompetent JEV lost these abilities, except for the ability to change microglial morphology. The bystander damage caused by activated glia also contributed to JEV-associated neurotoxicity. Microglia underwent morphological changes, increased cell proliferation and elevated TNF-alpha, IL-1beta, IL-6 and RANTES expression in response to JEV infection. In contrast, IL-6 and RANTES expression, but no apparent morphological changes, proliferation or TNF-alpha/IL-1beta expression, was demonstrated in JEV-infected astrocytes. Supernatants of JEV-infected microglia, but not JEV-infected astrocytes, induced glial activation and triggered neuronal death. Antibody neutralization studies revealed that TNF-alpha and IL-1beta, but not RANTES or IL-6, released by activated microglia appeared to play roles in JEV-associated neurotoxicity. In conclusion, following JEV infection, neuronal death was accompanied by concomitant microgliosis and astrogliosis, and neurotoxic mediators released by JEV-activated microglia, rather than by JEV-activated astrocytes, had the ability to amplify the microglial response and cause neuronal death.

Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring

Previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin (

Association between hematological parameters and metabolic syndrome components in a Chinese population

\hbox{HbA}_{{\rm 1c}}

Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies

) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring.

Manganese modulates pro-inflammatory gene expression in activated glia.

Insulin resistance, an essential core contributing to the metabolic syndrome (MS), has been demonstrated in some studies to be associated with white blood cell (WBC) or red blood cell (RBC) counts. The present study was undertaken to assess systemically the relationship between WBC or RBC counts and various clinical features of MS in a large Chinese population at Taiwan. A total of 4938 subjects (2891 men and 2047 women with a mean age of 50.1 +/- 12.6 years), who had attended health examination at this hospital were enrolled. The Adult Treatment Panel III (ATP III) definition of MS components was adopted in this study with the exception of the definition of obesity. This was defined as body mass index (BMI) greater than 27 kg/m(2). Overall, 14% had high serum total triglyceride (TG), 8% had low high-density lipoprotein (HDL) cholesterol, and 18% were obese. WBC counts showed a statistically significant (P < .001) correlation with TG (r = .265), HDL(r = -.187), fasting glucose (r = .084), and BMI (r = .172) but not with blood pressure levels. In addition, RBC counts correlated significantly (P < .001) with TG (r = .250), HDL(r = -.269), fasting glucose (r = .098), and BMI (r = .228). WBC and RBC counts in subjects grouped according to the presence of 0, 1, 2, and >or= 3 features of MS were 6268 +/- 1633, 6555 +/- 1782, 6995 +/- 1880, and 7185 +/- 1696 cells/mm(3), and 4.63 +/ -0.56 x 10(6), 4.73 +/- 0.54 x 10(6), 4.84 +/- 0.60 x 10(6), and 4.91 +/- 0.55 x 10(6) cells/mm(3), respectively (P for trend <.001). Subjects in the highest quartile of WBC or RBC counts demonstrated a three- or twofold increase, respectively, in the odds ratio for MS with 3 or more metabolic features compared to subjects in the lowest quartile of WBC or RBC counts. Increased WBC and RBC counts, albeit normal, were associated with a variety of MS features in a Taiwan Chinese population, suggesting that hematological parameters could potentially be used as indicators of this syndrome.

Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia

Objective Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated. Research Design and Methods Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored. Results The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10−18). Substantial heterogeneity was present (I2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10−4), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10−13), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10−5). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference. Conclusions A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.

Effects of Acarbose Versus Glibenclamide on Glycemic Excursion and Oxidative Stress in Type 2 Diabetic Patients Inadequately Controlled by Metformin: A 24-Week, Randomized, Open-Label, Parallel-Group Comparison

Redox-active metals are of paramount importance for biological functions. Their impact and cellular activities participate in the physiological and pathophysiological processes of the central nervous system (CNS), including inflammatory responses. Manganese is an essential trace element and it is required for normal biological activities and ubiquitous enzymatic reactions. However, excessive chronic exposure to manganese results in neurobehavioral deficits. Recent evidence suggests that manganese neurotoxicity involves activation of microglia or astrocytes, representative CNS immune cells. In this study, we assessed the molecular basis of the effects of manganese on the modulation of pro-inflammatory cytokines and nitric oxide (NO) production in primary rat cortical glial cells. Cultured glial cells consisted of 85% of astrocytes and 15% of microglia. Within the assayed concentrations, manganese was unable to induce tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression, whereas it potentiated iNOS and TNF-alpha gene expression by lipopolysaccharide/interferon-gamma-activated glial cells. The enhancement was accompanied by elevation of free manganese, generation of oxidative stress, activation of mitogen-activated protein kinases, and increased NF-kappaB and AP-1 binding activities. The potentiated degradation of inhibitory molecule IkappaB-alpha was one of underlying mechanisms for the increased activation of NF-kappaB by manganese. However, manganese decreased iNOS enzymatic activity possibly through the depletion of cofactor since exogenous tetrahydrobiopterin reversed manganeses action. These data indicate that manganese could modulate glial inflammation through variable strategies.

Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model

Microglial activation plays a pivotal role in the pathogenesis of neurodegenerative disease by producing excessive proinflammatory cytokines and nitric oxide (NO). Luteolin, a naturally occurring polyphenolic flavonoid antioxidant, has potent anti-inflammatory and neuroprotective properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation in microglia is not fully understood. In the present study, we report the inhibitory effect of luteolin on lipopolysaccharide (LPS)/interferon γ (IFN-γ)-induced NO and proinflammatory cytokine production in rat primary microglia and BV-2 microglial cells. Luteolin concentration-dependently abolished LPS/IFN-γ-induced NO, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) production as well as inducible nitric oxide synthase (iNOS) protein and mRNA expression. Luteolin exerted an inhibitory effect on transcription factor activity including nuclear factor κB (NF-κB), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF-1) in LPS/IFN-γ-activated BV-2 microglial cells. Biochemical and pharmacological studies revealed that the anti-inflammatory effect of luteolin was accompanied by down-regulation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt and Src. Further studies have demonstrated that the inhibitory effect of luteolin on intracellular signaling execution and proinflammatory cytokine expression is associated with resolution of oxidative stress and promotion of protein phosphatase activity. Together, these results suggest that luteolin suppresses NF-κB, STAT1 and IRF-1 signaling, thus attenuating inflammatory response of brain microglial cells.

Increased serum leptin concentrations correlate with soluble tumour necrosis factor receptor levels in patients with cirrhosis

BACKGROUND Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM. OBJECTIVE This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin. METHODS T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. β-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded. RESULTS A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. β-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12). CONCLUSIONS In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729.