Investigation of the Protective Effects of Taurine against Alloxan-Induced Diabetic Retinal Changes via Electroretinogram and Retinal Histology with New Zealand White Rabbits

The purpose of this study was to investigate the protective role of orally administered taurine against diabetic retinal changes via electroretinogram (ERG) and retinal histology on rabbits. Rabbits were randomly assigned into groups: Group I (vehicle administration only); Group II (diabetes: induced by 100 mg/kg alloxan injection); Group III (diabetes and fed with 200 mg/kg taurine); and Group IV (diabetes and fed with 400 mg/kg taurine). The body weight and blood glucose levels of the rabbits were monitored weekly. The ERG was measured on weeks 5 and 15. Retinal histology was analyzed in the end of the experiment. Results revealed that a taurine supplement significantly ameliorates the alloxan-induced hyperglycemia and protects the retina from electrophysiological changes. Group II showed a significant (P<0.05) change in the mean scotopic b-wave amplitude when compared to that of Group I, whereas the diabetic rabbits treated with taurine (Group III and IV) were analogous to Group I. Histologically, the amount of Bipolar and Müller cells showed no difference (P>0.05) between all groups and when compared with those of Group I. Our study provides solid evidences that taurine possesses an antidiabetic activity, reduced loss of body weight, and less electrophysiological changes of the diabetic retina

Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which leads to the motor control deficits. Recently, cell transplantation is a cutting-edge technique for the therapy of PD. Nevertheless, one key bottleneck to realizing such potential is allogenic immune reaction of tissue grafts by recipients. Cerebral dopamine neurotrophic factor (CDNF) was shown to possess immune-modulatory properties that benefit neurodegenerative diseases. We hypothesized that co-administration of CDNF with fetal ventral mesencephalic (VM) tissue can improve the success of VM replacement therapies by attenuating immune responses. Hemiparkinsonian rats were generated by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats, with/without CDNF administration. Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and smallanimal positron emission tomography (PET) coupled with [F-18] DOPA or [F-18] FE-PE2I, respectively. In addition, transplantation-related inflammatory response was determined by uptake of [F-18] FEPPA in the grafted side of striatum. Immunohistochemistry (IHC) examination was used to determine the survival of the grated dopaminergic neurons in the striatum and to investigate immune-modulatory effects of CDNF. The modulation of inflammatory responses caused by CDNF might involve enhancing M2 subset polarization and increasing fractal dimensions of 6-OHDA-treated BV2 microglial cell line. Analysis of CDNF-induced changes to gene expressions of 6-OHDA-stimulated BV2 cells implies that these alternations of the biomarkers and microglial morphology are implicated in the upregulation of protein kinase B signaling as well as regulation of catalytic, transferase, and protein serine/threonine kinase activity. The effects of CDNF on 6-OHDA-induced alternation of the canonical pathway in BV2 microglial cells is highly associated with PI3K-mediated phagosome formation. Our results are the first to show that CDNF administration enhances the survival of the grafted dopaminergic neurons and improves functional recovery in PD animal model. Modulation of the polarization, morphological characteristics, and transcriptional profiles of 6-OHDA-stimualted microglia by CDNF may possess these properties in transplantation-based regenerative therapies.Peer reviewe

Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which leads to the motor control deficits. Recently, cell transplantation is a cutting-edge technique for the therapy of PD. Nevertheless, one key bottleneck to realizing such potential is allogenic immune reaction of tissue grafts by recipients. Cerebral dopamine neurotrophic factor (CDNF) was shown to possess immune-modulatory properties that benefit neurodegenerative diseases. We hypothesized that co-administration of CDNF with fetal ventral mesencephalic (VM) tissue can improve the success of VM replacement therapies by attenuating immune responses. Hemiparkinsonian rats were generated by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats, with/without CDNF administration. Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small-animal positron emission tomography (PET) coupled with [18F] DOPA or [18F] FE-PE2I, respectively. In addition, transplantation-related inflammatory response was determined by uptake of [18F] FEPPA in the grafted side of striatum. Immunohistochemistry (IHC) examination was used to determine the survival of the grated dopaminergic neurons in the striatum and to investigate immune-modulatory effects of CDNF. The modulation of inflammatory responses caused by CDNF might involve enhancing M2 subset polarization and increasing fractal dimensions of 6-OHDA-treated BV2 microglial cell line. Analysis of CDNF-induced changes to gene expressions of 6-OHDA-stimulated BV2 cells implies that these alternations of the biomarkers and microglial morphology are implicated in the upregulation of protein kinase B signaling as well as regulation of catalytic, transferase, and protein serine/threonine kinase activity. The effects of CDNF on 6-OHDA-induced alternation of the canonical pathway in BV2 microglial cells is highly associated with PI3K-mediated phagosome formation. Our results are the first to show that CDNF administration enhances the survival of the grafted dopaminergic neurons and improves functional recovery in PD animal model. Modulation of the polarization, morphological characteristics, and transcriptional profiles of 6-OHDA-stimualted microglia by CDNF may possess these properties in transplantation-based regenerative therapies

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage

Background/Aims: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. Methods: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Results: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice. Conclusion: MRE exhibited antiinflammatory and hepatic protective activity

Functional roles of arginine residues in mung bean vacuolar H+-pyrophosphatase

AbstractPlant vacuolar H+-translocating inorganic pyrophosphatase (V-PPase EC 3.6.1.1) utilizes inorganic pyrophosphate (PPi) as an energy source to generate a H+ gradient potential for the secondary transport of ions and metabolites across the vacuole membrane. In this study, functional roles of arginine residues in mung bean V-PPase were determined by site-directed mutagenesis. Alignment of amino-acid sequence of K+-dependent V-PPases from several organisms showed that 11 of all 15 arginine residues were highly conserved. Arginine residues were individually substituted by alanine residues to produce R→A-substituted V-PPases, which were then heterologously expressed in yeast. The characteristics of mutant variants were subsequently scrutinized. As a result, most R→A-substituted V-PPases exhibited similar enzymatic activities to the wild-type with exception that R242A, R523A, and R609A mutants markedly lost their abilities of PPi hydrolysis and associated H+-translocation. Moreover, mutation on these three arginines altered the optimal pH and significantly reduced K+-stimulation for enzymatic activities, implying a conformational change or a modification in enzymatic reaction upon substitution. In particular, R242A performed striking resistance to specific arginine-modifiers, 2,3-butanedione and phenylglyoxal, revealing that Arg242 is most likely the primary target residue for these two reagents. The mutation at Arg242 also removed F− inhibition that is presumably derived from the interfering in the formation of substrate complex Mg2+–PPi. Our results suggest accordingly that active pocket of V-PPase probably contains the essential Arg242 which is embedded in a more hydrophobic environment

A population study on the association between leisure time physical activity and self-rated health among diabetics in Taiwan

<p>Abstract</p> <p>Background</p> <p>There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.</p> <p>Methods</p> <p>Data came from the 2001 Taiwan National Health Interview Survey (NHIS). Inclusion criteria were a physician confirmed diagnosis of diabetes mellitus and age 18 years and above (n = 797). Self-rated health was assessed by the question "In general, would you say that your health is excellent, very good, good, fair, or poor?" Individuals with a self perceived health status of good, very good, or excellent were considered to have positive health status.</p> <p>Results</p> <p>In the full model, the odds ratio (OR) for positive health was 2.51(95% CI = 1.53-4.13), 1.62(95% CI = 0.93-2.84), and 1.35(95% CI = 0.77-2.37), for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. Those with duration over 10 years (OR = 0.53, 95%CI = 0.30-0.94), heart disease (OR = 0.50, 95%CI = 0.30-0.85), and dyslipidemia (OR = 0.65, 95% CI = 0.43-0.98) were less likely to have positive health than their counterparts. After stratified participants by duration, those with a duration of diabetes < 6 years, the adjusted OR for positive health was 1.95(95% CI = 1.02-3.72), 1.22(95% CI = 0.59-2.52), and 1.19(95% CI = 0.58-2.41) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. In participants with a duration of diabetes ≥ 6 years, total energy expenditure showed a gradient effect on self-perceived positive health. The adjusted OR for positive health was 3.45(95% CI = 1.53-7.79), 2.77(95% CI = 1.11-6.92), and 1.90(95% CI = 0.73-4.94) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals.</p> <p>Conclusions</p> <p>Our results highlight that regular leisure activity with an energy expenditure ≧ 500 kcal per week is associated with better self-rated health for those with longstanding diabetes.</p