Abelmoschus esculentus (Okra) Prevents Insulin Resistance and Restores Neuron Autophagy by Regulating Dipeptidyl Peptidase-4 and Thus Improving Hippocampal Function.

Diabetes is highly linked to the occurrence of Alzheimer disease (AD), which is characterized by beta amyloid peptide (Aß) and hyperphosphorylation of tau (p-tau), and neuron damage particularly in hippocampus. Type 2 diabetes (T2D) is featured by insulin resistance, and phosphorylation of Ser307-IRS-1 is regarded as a resistance marker. Inhibitors of dipeptidyl peptidase-4 (DPP-4) are effective tools for treating T2D. Previously, we reported subfractions of Abelmoschus esculentus (AE, okra) (F1 rich in quercetin glycosides; F2 composed of polysaccharide) attenuated DPP-4 and its downstream signals of insulin resistance, thus preventing Aß-induced neuron damage. Since autophagy could be protective, we now explore if AE works to modulate neuron autophagy by regulating DPP-4 and insulin resistance and, thus, improves the hippocampal function and behavior. We demonstrated that AE subfractions attenuate Aß-induced insulin resistance and the expression of p-tau and normalize the autophagy and survival of hippocampal neurons. The action of AE may be attributed to the downregulation of DPP-4, which plays a critical role in mediating insulin resistance and hinders neuron autophagy. The in vivo findings reveal that the hippocampal insulin resistance appears to link with loss of memory, reduction of curiosity, and depression, whereas treatment with AE significantly improves the insulin sensitivity and hippocampal function. Noteworthy, even at only 5 µg/mL, F2 seems to exhibit a meaningful effect. In conclusion, we suggest that AE attenuates insulin resistance and recovers neuron autophagy which are regulated by DPP-4, thus preventing the damage to the hippocampus, improving recognition and emotion. AE may be an effective adjuvant or supplement to prevent insulin resistance-associated pathogenesis of AD if these results can be confirmed in human clinical trials.

Abelmoschus esculentus subfractions ameliorate hepatic lipogenesis and lipid uptake via regulating dipeptidyl peptidase-4-With improving insulin resistance.

Nonalcoholic fatty liver disease (NAFLD) is recognized as the liver component of metabolic syndrome. The regulation of hepatic lipid should be emphasized to prevent accompanying illness. As AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP) regulate lipid metabolism, CD36 and fatty acid synthase (FAS) promote lipid uptake and lipogenesis respectively, while acetyl-CoA carboxylase (ACC) is an indicator of negative feedback. The increase of IRS-1 phosphorylation at the residue ser307 (p-ser307-IRS-1) and decrease of p-ser473-Akt (p-Akt) are viewed as the insulin resistance markers, and our previous reports suggested dipeptidyl peptidase-4 (DPP-4) mediates insulin resistance, the crucial factor of metabolic syndrome. Abelmoschus esculentus (AE) fruit is well-known for its antidiabetic utility. We had isolated several AE subfractions by successive steps, and found that F1 and F2 were especially valid in suppressing DPP-4 signaling. Since little is known if AE works on NAFLD, now we first attempt to investigate whether AE is useful to attenuate hepatic lipogenesis and lipid uptake in liver cells, along with improving the metabolic targets. We demonstrated that AE subfractions attenuated the hepatic lipid accumulation induced by free fatty acids. Treatment of AE alleviated FAS and returned the level of p-ser79-ACC (p-ACC). Although F1 was more effective on AMPK, F2 seemed more stable to attenuate SREBP-1. Moreover, as fatty acids stimulated the expression of CD36, F2 showed a superior effect to down-regulate the lipid uptake. Both AE subfractions reduced the generation of ROS, decreased the level of p-ser307-IRS-1, and restored the expression of p-Akt. Moreover, treatment of DPP-4 inhibitor linagliptin revealed that, AE could prevent the hepatic lipogenesis, oxidative burden, and the related insulin resistance via downregulating DPP-4. In conclusion, the present investigation revealed that AE, especially F2, is potential to be developed as adjuvant to prevent NAFLD.

Abelmoschus esculentus subfractions attenuate Aß and tau by regulating DPP-4 and insulin resistance signals.

BACKGROUND: Insulin resistance could be associated with the development of Alzheimer disease (AD). The neuropathological hallmarks of AD are beta amyloid (Aß) produced from sequential cleavage initiated by ß-secretase and degraded by insulin degradation enzyme (IDE), as well as hyperphosphorylation of tau (p-tau). Insulin action involves the cascades of insulin receptor substrates (IRS) and phosphatidylinositol 3-kinase (PI3K), while phosphorylation of IRS-1 at ser307 (p-ser307IRS-1) hinders the response. Our previous report suggested dipeptidyl peptidase-4 (DPP-4) is crucial to insulin resistance, and the subfractions of Abelmoschus esculentus (AE), F1 and F2, attenuate the signaling. Here we aim to investigate whether AE works to reduce Aß generation via regulating DPP4 and insulin resistance. METHODS: The subfractions F1 and F2 were prepared according to a succession of procedures. F1 was composed by quercetin glycosides and triterpene ester, and F2 contained a large amount of polysaccharides. The in vitro insulin resistance model was established by SK-N-MC cell line treated with palmitate. MTT was used to define the dose range, and thereby Western blot, ELISA, and the activity assay were used to detect the putative markers. One-way ANOVA was performed for the statistical analysis. RESULTS: Treatment of palmitate induced the level of p-ser307IRS-1. Both F1 and F2 effectively decrease p-ser307IRS-1, and recover the expression of p-PI3K. However, the expression of total IRS plunged with 25 µg/mL of F1, while descended steadily with 5 µg/mL of F2. As palmitate increased the levels of Aß40 and Aß42, both AE subfractions were effective to reduce Aß generation of and ß-secretase activity, but IDE was not altered in any treatment conditions. The expression of DPP4 was also accompanied with insulin resistance signals. Inhibition of DPP4 attenuated the activity of ß-secretase and production of Aß. Moreover, the present data revealed that both AE subfractions significantly decrease the level of p-Tau. CONCLUSIONS: In conclusion, we demonstrated that AE would be a potential adjuvant to prevent insulin resistance and the associated pathogenesis of AD, and F2 seems more feasible to be developed.

Solanum nigrum polyphenols reduce body weight and body fat by affecting adipocyte and lipid metabolism.

Obesity, being overweight and deposition of body fat are critically associated with metabolic disorders. The number of adipocytes and their lipid content, and the molecules involved in lipid metabolism are involved in obesity comorbidity. The food, Solanum nigrum L. (SN), has medical benefits in many aspects. In our recent report, SN was shown to reduce hepatic fat accumulation and oxidative stress, thus attenuating liver damage. However, it has not yet been explored whether SN is effective for weight loss and body fat reduction. Hence, we aimed to investigate if SN water extract (SWE) and the derived polyphenols (SNPE) are able to prevent obesity. Mice fed a high fat diet (HFD) and 3T3L1 cells model were used. The in vivo experiments showed SWE decreased serum triacylglyceride, cholesterol, and low-density lipoprotein (LDL)-cholesterol induced by a HFD. SWE promoted hepatic lipolysis by increasing PPARα and CPT-1, and inhibited lipogenesis by decreasing FaS and HMG-CoR. The expression of AMPK was enhanced, but sterol regulatory element binding proteins (SREBPs) were reduced by SWE, especially at 5%. In vitro analysis revealed that SNPE decreased the amount and lipid content of adipocytes. SNPE, especially at 0.5 mg mL-1, promoted lipolysis while inhibiting lipogenesis. In comparison with the doses applied in vivo and in vitro, the effect of SN could be attributed to the composition of the polyphenols. The results showed that SNPE is suggested to be an anti-obesity agent that is able to reduce body weight and body fat, by decreasing the amount and lipid content of adipocytes, and regulating lipid metabolism.

Abelmoschus esculentus subfractions attenuate beta amyloid-induced neuron apoptosis by regulating DPP-4 with improving insulin resistance signals.

The association of Alzheimer disease (AD) and Diabetes (DM) is less clear. Accumulation of beta amyloid (Aß) and presence of hyperphosphorylated tau (p-tau) are hallmarks of AD, spreading in the region where insulin receptors are also found. Aß exerts neuron toxicity, and could disturb insulin signaling of phosphatidylinositol 3-kinase (PI3K), glycogen synthase kinase (GSK)-3ß and AMP-activated protein kinase (AMPK), but increase IRS-1-Ser307 phosphorylation which is viewed as insulin resistance marker. Previously we reported dipeptidyl peptidase-4 (DPP-4) mediate insulin resistance signals, and Abelmoschus esculentus (AE) subfractions F1 (rich in quercetin glucosides and triterpene ester) and F2 (containing large amount of polysaccharides) attenuate DPP-4-mediated apoptosis. In the present study, we aim to investigate if Aß induce neuron death by regulating DPP-4 and insulin resistance signals, and the putative effect of F1 and F2. By MTT, microscopy, and Western blotting, we demonstrate treatment of appropriate doses of AE subfractions prevent Aß-induced neuron apoptosis. F1 attenuate Aß-induced caspase 3 expression especially at 25 µg/mL, while F2 attenuate caspase 3 activation even at the low dose of 1 µg/mL. Both AE subfractions decrease Aß-enhanced DPP-4, but increase Aß-reduced p-AMPK and p-PI3K. The activity analysis reveals that F2 is more valid than F1 to reduce DPP-4 activity. The inhibition of DPP-4 demonstrates it plays the pivotal role in Aß-induced neuron apoptosis. Moreover, although both F1 and F2 are effective to inhibit p-IRS-1-Ser307, F2 takes advantage to reduce p-Tau while F1 is superior to enhance p-GSK-3ß. This implies AE subfractions act on different targets, and could be developed respectively. In conclusion, we demonstrate AE is potential to prevent Aß-induced neuron damage by regulating DPP-4 and the insulin resistance cascades. AE could be an adjuvant to protect neuron degenerative disease related to Aß and insulin resistance.

Abelmoschus esculentus subfractions improved nephropathy with regulating dipeptidyl peptidase-4 and type 1 glucagon-like peptide receptor in type 2 diabetic rats.

Abelmoschus esculentus (AE) has been used in traditional medicine to ameliorate hyperglycemia, but its mucilage increased bioassay difficulties. We have obtained a series of AE subfractions. Among them F1 and F2 regulated dipeptidyl peptidase-4 (DPP-4) and type 1 glucagon-like peptide receptor (GLP-1R), the treatment targets for type 2 diabetes. F1, F2 and fraction residues (FR) showed advantage on different aspects, which attenuates insulin resistance and metabolic disorder in vivo, and prevents renal-tubular change in vitro. In the present study, using type 2 diabetes model induced by high fat diet (HFD) and streptozotocin (STZ), we aim to investigate whether AE prevent diabetic nephropathy by regulating the putative markers. The results showed that all the subfractions ameliorated albuminuria and renal hyperfiltration (measured by creatinine clearance rate; CCr) accompanied with diabetes, while F2 acted most promptly and consistently. Histologically AE reduced renal tubular change, fibrosis and fat deposition. F2 and FR exerted significant effects to decrease DPP-4 while increase GLP-1R. Although all the subfractions were effective to reduce oxidative stress, only F2 acted on kidneys specifically. In conclusion, we have demonstrated AE has benefits to regulate DPP-4 and GLP-1R, to reduce oxidative stress and renal fibrosis, with resultant to improve renal function and prevent diabetic renal damage. Taken together, F2 could be more promising to be developed as adjuvant for diabetic nephropathy.

Liraglutide protects against glucolipotoxicity-induced RIN-m5F ß-cell apoptosis through restoration of PDX1 expression.

Prolonged exposure to high levels of glucose and fatty acid (FFA) can induce tissue damage commonly referred to as glucolipotoxicity and is particularly harmful to pancreatic ß-cells. Glucolipotoxicity-mediated ß-cell failure is a critical causal factor in the late stages of diabetes, which suggests that mechanisms that prevent or reverse ß-cell death may play a critical role in the treatment of the disease. Transcription factor PDX1 was recently reported to play a key role in maintaining ß-cell function and survival, and glucolipotoxicity can activate mammalian sterile 20-like kinase 1 (Mst1), which, in turn, stimulates PDX1 degradation and causes dysfunction and apoptosis of ß-cells. Interestingly, previous research has demonstrated that increased glucagon-like peptide-1 (GLP-1) signalling effectively protects ß cells from glucolipotoxicity-induced apoptosis. Unfortunately, few studies have examined the related mechanism in detail, especially the role in Mst1 and PDX1 regulation. In the present study, we investigate the toxic effect of high glucose and FFA levels on rat pancreatic RINm5F ß-cells and demonstrate that the GLP-1 analogue liraglutide restores the expression of PDX1 by inactivating Mst1, thus ameliorating ß-cell impairments. In addition, liraglutide also upregulates mitophagy, which may help restore mitochondrial function and protect ß-cells from oxidative stress damage. Our study suggests that liraglutide may serve as a potential agent for developing new therapies to reduce glucolipotoxicity.

Soy-Based Foods Are Negatively Associated with Cognitive Decline in Taiwan's Elderly.

Cognitive impairment is a common neurodegenerative disease in the elderly. Dietary factors have an important role in cognitive dysfunction. Soy has many benefits, and consumption of soy-based foods is general in East Asian countries. In this study, we want to investigate the association between cognitive function decline and soy-based food intake among the elderly in Taiwan. This cross-sectional study was based on data obtained from the 2005-2008 Nutrition and Health Survey in Taiwan (NAHSIT). Subjects aged less than 65 y or with missing data were excluded. There was a total of 1,105 participants aged 65 and over who completed Short Portable Mental Status Questionnaire (SPMSQ). Eighty-five-point-six percent of participants consumed soy-based foods every day. After adjustment for potential variables, the logistic regression model showed significant associations for age, gender, education, soy-based foods intake and physical component summary (PCS). Age and female gender were both positively correlated with cognitive impairment (odds ratios: 1.1 and 4.43, respectively). Furthermore, there were negative correlations for education, soy-based foods intake and PCS (odds ratios: 0.25, 0.45 and 0.97, respectively). In this study, we found that soy-based foods were negatively associated with cognitive function decline among Taiwanese elderly. This result may be used as a reference for dietary advice for the elderly.

Progress of diabetes severity associated with severe hypoglycemia in Taiwan.

OBJECTIVES: The association between the progression of diabetes severity and risk of severe hypoglycemia is unknown. This study aimed to evaluate the association between the progression of diabetes severity and severe hypoglycemia in patients with diabetes. STUDY DESIGN: A 13-year population-based retrospective cohort study of patients with diabetes in Taiwan. METHODS: Diabetes progression was evaluated by the adapted Diabetes Complications Severity Index (aDCSI) score from index date to end of follow-up. The progression of diabetes severity was divided into 3 categories: slow, moderate, and rapid increase in aDSCI score. We further compared those 3 categories and evaluated the risk of first hospitalization due to severe hypoglycemia. RESULTS: A total of 330,831 patients with diabetes were recruited. The mean age of patients in this study was 56.8 years, and mean follow-up duration was 9.3 years. The mean initial aDCSI score was 0.7, whereas the mean aDCSI score at the event date or end date was 2.9. A rapid increase in aDCSI score was associated with higher risk of severe hypoglycemia compared with a slow increase (hazard ratio, 4.91; 95% CI, 4.65-5.18). The incidence densities of severe hypoglycemia (per 1000 person-years) for slow, moderate, and rapid increase in aDCSI score were 2.3, 2.5, and 11.4, respectively. CONCLUSIONS: This study demonstrated that rapid progression of diabetes complications was associated with higher risk of severe hypoglycemia. It is imperative that treating physicians identify patients with acute worsening of diabetes severity and provide proper hypoglycemia education and prevention care.

Mulberry Leaf Extracts prevent obesity-induced NAFLD with regulating adipocytokines, inflammation and oxidative stress.

Mulberry (Morus alba) leaf has been used in Chinese medicine as the remedy for hyperlipidemia and metabolic disorders. Recent report indicated Mulberry leaf extract (MLE) attenuated dyslipidemia and lipid accumulation in high fat diet (HFD)-fed mice. Non-alcoholic fatty liver (NAFLD) is generally considered as the liver component of metabolic syndrome. The hepatic lipid infiltration induces oxidative stress, and is associated with interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) which are regulated by the leptin and adiponectin. MLE could prevent obesity-related NAFLD via downregulating the lipogenesis enzymes while upregulating the lipolysis markers. Treatment of MLE, especially at 2%, enhanced the expression of superoxide dismutase (SOD) and clenched the oxidative stress of liver. MLE decreased the plasma level of leptin but increased adiponectin. The advantage of MLE is supposed mainly attributed to chlorogenic acid derivative. We suggest MLE, with promising outcome of research, could be nutraceutical to prevent obesity and related NAFLD.

The nutraceutical benefits of subfractions of Abelmoschus esculentus in treating type 2 diabetes mellitus.

Abelmoschus esculentus (AE), a commonly consumed vegetable, is well-known for its anti-hyperglycemic effects. However, few scientific reports have identified its targets because mucilage increases the difficulty of manipulation. We recently reported extraction steps to obtain subfractions of AE, which were found to attenuate the adverse effects of high glucose and fatty acid in vitro. In this study, we used modified extraction steps and type 2 diabetic rats to explore whether AE subfractions can improve the metabolic disturbances caused by insulin resistance in vivo. AE subfractions (F1, F2, and FR) were prepared. The type 2 diabetes model was induced by feeding male Sprague-Dawley rats with a high-fat diet and injecting them with 35 mg/kgbw streptozotocin when their body weight reached 475 ± 15 g. After a hyperglycemic status had been confirmed, the rats were tube-fed with or without different doses of AE subfractions. Serum glucose, lipid markers, insulin, HbA1c and HOMA-IR were measured in the following 12 weeks. Serum glucose promptly increased and insulin resistance was noted in the diabetic rats (glucose: 360-500 mg/dl, HOMA-IR 9.8-13.8). F2, rich in polysaccharides and carbohydrates, was most effective in attenuating hyperglycemia and insulin resistance (glucose: 200 mg/dl; HOMA-IR: 5.3) and especially HbA1C (from 8.0% to 6.5%). All of the AE subfractions lowered the level of triglycerides and free fatty acid, but not the level of total cholesterol. FR significantly increased the high-density lipoprotein/low-density lipoprotein ratio, indicating its benefits for lipoprotein profiles. While F2 and FR were associated with weight gain, F1 possessed an anti-obese effect. In conclusion, whether it is consumed as a vegetable or as a nutraceutical, AE has the potential to be an adjuvant therapy for diabetes. AE subfractions could be developed individually and deserve further investigation.

Mevastatin promotes neuronal survival against Aß-induced neurotoxicity through AMPK activation.

Statins or HMG-CoA reductase inhibitors have been shown to be effective at lowering cholesterol levels, and the application of these molecules has gradually emerged as an attractive therapeutic strategy for neurodegenerative diseases. Epidemiological studies suggest that statin use is associated with a decreased incidence of Alzheimer's disease (AD). Thus, statins may play a beneficial role in reducing amyloid ß (Aß) toxicity, the most relevant pathological feature and pathogenesis of AD. However, the precise mechanisms involved in statin-inhibited Aß toxicity remain unclear. In the present study, we report that mevastatin significantly protects against Aß-induced neurotoxicity in SK-N-MC neuronal cells by restoring impaired insulin signaling. This protection appears to be associated with the activation of AMP-activated protein kinase (AMPK), which has long been known to increase insulin sensitivity. Our results also indicate that high levels of cholesterol likely underlie Aß-induced neurotoxicity and that activation of AMPK by mevastatin alleviates insulin resistance. Signaling through the insulin receptor substrate-1/Akt pathway appears to lead to cell survival. These findings demonstrate that mevastatin plays a potential therapeutic role in targeting Aß-mediated neurotoxicity. The molecule presents a novel therapeutic strategy for further studies in AD prevention and therapeutics.

Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced ß cell apoptosis via inhibiting dipeptidyl peptidase-4.

Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of ß cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect ß cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect. In our recent report, a sequence of extraction steps was used to obtain a series of subfractions from AE, each with its own composition and property. Among them F1 (rich in quercetin glucosides and pentacyclic triterpene ester) and F2 (containing large amounts of carbohydrates and polysaccharides) were found to be especially effective in attenuating DPP-4 signaling, and to have the potential to counter diabetic nephropathy. Hence, the aim of the present study was to investigate whether AE subfractions can prevent the palmitate-induced apoptosis of ß cells, and the putative signals involved. We demonstrated that AE, and especially 1 µg/mL of F2, decreased palmitate-induced apoptosis analyzed by flow cytometry. The result of western blot revealed that palmitate-induced decrease in GLP-1R and increase in DPP-4 were restored by F1 and F2. The DPP-4 inhibitor linagliptin decreased the expression of caspase 3, suggesting that DPP-4 is critically involved in apoptotic signaling. Analysis of enzyme activity revealed that palmitate increased the activity of DPP4 nearly 2 folds, while F2 especially inhibited the activation. In addition, AMPK/mTOR, PI3K and mitochondrial pathways were regulated by AE, and this attenuated the palmitate-induced signaling cascades. In conclusion, AE is useful to prevent the exacerbation of ß cell apoptosis, and it could potentially be used as adjuvant or nutraceutical therapy for diabetes.

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

PURPOSE: Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. METHODS: This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. RESULTS: We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (<8,600 mg) and medium (8,600-88,900 mg) cumulative doses of aspirin did not reduce the risk of breast cancer. CONCLUSIONS: Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Periodontal Treatment and the Risks of Cardiovascular Disease in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Objective Periodontal disease may predispose individuals to cardiovascular disease (CVD). Diabetes mellitus, especially in patients with severe periodontitis, increases the risk of CVD mortality. However, the outcomes of periodontal therapy vary among the different treatment modalities. We aim to investigate whether periodontal treatment could influence the occurrence of CVD in patients with type 2 diabetes and periodontal problems. Methods A retrospective cohort study was conducted based on a dataset released by Taiwan National Health Insurance (NHI). The dataset was composed of randomly sampled, newly diagnosed diabetic patients who received insurance benefits from 1999 to 2001; patients who were younger than 18 years of age or who already had CVD before 1999 were excluded. The NHI code was used to identify the treatments, including subgingival curettage and flap operations. The patients' demographic variables were matched using a 1:4 propensity score. All of the subjects were followed up until the onset of CVD, or December 31, 2011. A Cox proportional hazards regression analysis was performed to evaluate the effects of periodontal treatment on the rates of myocardial infarction, heart failure and stroke. Results Three thousand thirty-nine and 12,156 diabetic subjects were classified into the advanced periodontal treatment group and the non-advanced periodontal treatment group, respectively. The Cox proportional hazards analysis revealed that although the overall incidence of CVD was not significantly improved (Hazard ratio, HR 0.95; 95% CI 0.90-1.01), advanced periodontal treatment reduced the rates of myocardial infarction (HR 0.92; 95% CI 0.85-0.99) and heart failure (HR 0.60; 95% CI 0.45-0.80). There was no significance difference in the incidence of stroke (HR 0.95; 95% CI 0.85-1.06). Conclusion Advanced periodontal therapy lowers the rate of CVD, especially myocardial infarction and heart failure. Dental management has a beneficial effect on the health of patients with type 2 diabetes.

Antrodia cinnamomea Prevents Obesity, Dyslipidemia, and the Derived Fatty Liver via Regulating AMPK and SREBP Signaling.

Antrodia cinnamomea (AC), a protogenic fungus that only grows on the heartwood of endemic Cinnamomum kanehirae Hayata in Taiwan, is used to treat a variety of illness including liver disease. However, little is known about the benefit of AC against obesity and the related hepatic disorder. Using high-fat-diet (HFD) feed mice, we aimed to investigate whether the extract of AC (ACE) could reduce excessive weight, body fat, and serum lipids and prevent the development of non-alcoholic fatty liver (NAFLD). C57BL/6 mice were divided into five groups fed with different diets: control, HFD, and HFD with 0.5%, 1%, or 2% of ACE, respectively. After 10 weeks the animals were sacrificed, with serum and liver collected. HFD-induced elevation of body weight gain, body fat deposition, and serum free fatty acid (FFA), triacylglycerol (TGs), total cholesterol, and ratio of LDL cholesterol (LDL-C)/HDL cholesterol (HDL-C), were significantly restored by ACE. ACE reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic lipid deposits increased by HFD. ACE increased p-AMP activated protein kinase (pAMPK) but decreased Sterol regulatory element binding protein (SREBP), fatty acid synthase (FAS), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), and 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. The chemical analysis reveals ACE is full of triterpenes, the most abundant of which is Antcin K, followed by sulphurenic acid, eburicoic acid, antcin C, dehydrosulphurenic acid, antcin B, and propanoic acid. In conclusion, ACE should be used to prevent obesity and derived fatty liver. The applicability of ACE on NAFLD deserves further investigation.

Iodinated Contrast Media-Induced Thyroid Dysfunction in Euthyroid Nodular Goiter Patients.

BACKGROUND: The risks of thyroid dysfunction after iodinated contrast media exposure in patients with euthyroid nodular goiter are largely unknown. METHODS: This observational, retrospective cohort study included a random selection of one million people in Taiwan. All patients with iodinated contrast media exposure during this study period were selected. Patients with euthyroid nodular goiter were identified as cases, while patients without thyroid nodule were selected as controls. We followed these patients until the first event of thyroid dysfunction including hyperthyroidism or hypothyroidism after iodinated contrast media exposure. RESULTS: A total of 334 cases and 2672 matched controls were selected in this study. The mean age of cases and controls were 58.6 and 58.4 years old, and mean follow-up durations were 2.1 and 2 years respectively. After adjustment, patients with euthyroid nodular goiter had a higher risk of thyroid dysfunction (hazard ratio 5.43, [confidence interval (CI) 3.01-9.80]) compared with controls after iodinated contrast media exposure. In the subgroup analysis, the risks of hyperthyroidism and hypothyroidism in cases compared with controls were 5.77 [CI 2.64-12.62] and 4.95 [CI 2.15-11.40] respectively. Half of the euthyroid nodular goiter cases developed thyroid dysfunction within one year after iodinated contrast media exposure. Interestingly, all thyroid-related comorbidities and drug prescriptions did not increase the risk of thyroid dysfunction. CONCLUSIONS: Presence of euthyroid nodular goiter was associated with higher risk of thyroid dysfunction including hyperthyroidism and hypothyroidism after iodinated contrast media exposure.

Comparison of Different Models of Structured Self-Monitoring of Blood Glucose in Type 2 Diabetes.

BACKGROUND: The aim of this study is to compare the effectiveness of different models of structured self-monitoring of blood glucose (SMBG) in non-insulin-treated type 2 diabetes. SUBJECTS AND METHODS: This was a prospective, three-arm, randomized, 36-week trial. There were 138 participants with a mean age of 58.7 years and glycated hemoglobin A1c (HbA1c) level of 8.72% who were allocated to the following groups: six-pair glucose test of pre- and postprandial blood glucose (BG) per week (n = 43); three-pair glucose test of pre- and postprandial BG per week (n = 39); and seven-point BG testing before and after each meal and at bedtime over a course of 3 days in 1 month (n = 40). RESULTS: The intention-to-treat analysis revealed that all three groups showed significant reductions in HbA1c levels. Comparisons among the groups revealed that only the seven-point group had a significant greater reduction of HbA1c level compared with the three-pair group (between-group mean difference of -0.86 and -0.80 from baseline to 24 and 36 weeks, respectively). No severe hypoglycemic events were reported. Diabetes distress was slightly higher in the six-pair group. CONCLUSIONS: Our results demonstrated that BG testing at six pairs/week, three pairs/week, and seven points for 3 days/month were all effective in improving glycemic outcome, with greater reduction of HbA1c level in the seven-point for 3 days/month group, without increasing burdensome distress in SMBG.

Abelmoschus esculentus fractions potently inhibited the pathogenic targets associated with diabetic renal epithelial to mesenchymal transition.

Although Abelmoschus esculentus (AE) is known for anti-hyperglycemia, few reports have addressed its target. Our recent studies have focused on diabetic renal epithelial to mesenchymal transition (EMT), which plays a critical role in fibrosis that accompanies increasing vimentin and suggested signals DPP-4/AT-1/TGF-ß1. This study aimed to investigate whether AE is useful for preventing diabetic renal EMT. We used a succession of extractions and obtained the corresponding fractions F1-F5, each with its own individual properties: F1 inhibits high glucose-stimulated vimentin, AT-1, TGF-ß1, and DPP-4, and recovers E-cadherin in tubular cells; F2 decreases high glucose-induced vimentin, AT-1 and DPP-4; F3-F5 do not reduce the expression of vimentin. Chemical analysis revealed that F1 is rich of flavonoid glycosides especially quercetin glucosides, and pentacyclic triterpene ester. F2 contains a large amount of carbohydrates and polysaccharides composed of uronic acid, galactose, glucose, myo-inositol etc. In conclusion, AE has the potential to serve as an adjuvant for diabetic nephropathy, with F1 and F2 especially deserving further investigation and development.

Epigallocatechin gallate attenuates amyloid ß-induced inflammation and neurotoxicity in EOC 13.31 microglia.

Microglia are the primary immune cells that contribute to neuroinflammation by releasing various proinflammatory cytokines and neurotoxins in the brain. Microglia-mediated neuroinflammation is one of the key characteristics of Alzheimer's disease (AD). Therefore, inhibitory reagents that prevent microglial activation may be used as potential therapeutic agents for treating AD. Recently, many studies have been performed to determine the bioactivities of green tea polyphenol epigallocatechin-3-gallate (EGCG), an efficient antioxidant that prevents neuroinflammation. However, limited information is available on the effects of EGCG on microglia-mediated neuroinflammation. In this study, we investigated the inhibitory effects of EGCG on amyloid ß (Aß)-induced microglial activation and neurotoxicity. Our results indicated that EGCG significantly suppressed the expression of tumor necrosis factor α (TNFα), interleukin-1ß, interleukin-6, and inducible nitric oxide synthase (iNOS) in Aß-stimulated EOC 13.31 microglia. EGCG also restored the levels of intracellular antioxidants nuclear erythroid-2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thus inhibiting reactive oxygen species-induced nuclear factor-κB (NF-κB) activation after Aß treatment. Furthermore, EGCG effectively protected neuro-2a neuronal cells from Aß-mediated, microglia-induced cytotoxicity by inhibiting mitogen-activated protein kinase-dependent, Aß-induced release of TNFα. Taken together, our findings suggested that EGCG suppressed Aß-induced neuroinflammatory response of microglia and protected against indirect neurotoxicity. These results suggest that EGCG is a possible therapeutic agent for preventing Aß-induced inflammatory neurodegeneration.