Tai-chi for residential patients with schizophrenia on movement coordination, negative symptoms, and functioning: a pilot randomized controlled trial

Objective. Patients with schizophrenia residing at institutions often suffer from negative symptoms, motor, and functional impairments more severe than their noninstitutionalized counterparts. Tai-chi emphasizes body relaxation, alertness, and movement coordination with benefits to balance, focus, and stress relief. This pilot study explored the efficacy of Tai-chi on movement coordination, negative symptoms, and functioning disabilities towards schizophrenia. Methods. A randomized waitlist control design was adopted, where participants were randomized to receive either the 6-week Tai-chi program and standard residential care or only the latter. 30 Chinese patients with schizophrenia were recruited from a rehabilitation residency. All were assessed on movement coordination, negative symptoms, and functional disabilities at baseline, following intervention and 6 weeks after intervention. Results. Tai-chi buffered from deteriorations in movement coordination and interpersonal functioning, the latter with sustained effectiveness 6 weeks after the class was ended. Controls showed marked deteriorations in those areas. The Tai-chi group also experienced fewer disruptions to life activities at the 6-week maintenance. There was no significant improvement in negative symptoms after Tai-chi. Conclusions. This study demonstrated encouraging benefits of Tai-chi in preventing deteriorations in movement coordination and interpersonal functioning for residential patients with schizophrenia. The ease of implementation facilitates promotion at institutional psychiatric services.published_or_final_versio

Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans

Context: Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state. Methods: Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA. Results: Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point. Conclusion: Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state.Leonie K. Heilbronn, Lesley V. Campbell, Aimin Xu, Dorit Samocha-Bone

Identification of a Novel Substance P–Neurokinin-1 Receptor MicroRNA-221-5p Inflammatory Network in Human Colonic Epithelial Cells

Background & AimsSubstance P (SP), a neuropeptide member of the tachykinin family, plays a critical role in colitis. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. We examined whether SP modulates expression of microRNAs in human colonic epithelial cells.MethodsWe performed microRNA profiling analysis of SP-stimulated human colonic epithelial NCM460 cells overexpressing neurokinin-1 receptor (NCM460-NK-1R). Targets of SP-regulated microRNAs were validated by real-time polymerase chain reaction (RT-PCR). Functions of miRNAs were tested in NCM460-NK-1R cells and the trinitrobenzene sulfonic acid (TNBS) and dextran sulfate sodium (DSS) models of colitis.ResultsSP stimulated differential expression of 29 microRNAs, including miR-221-5p, the highest up-regulated miR (by 12.6-fold) upon SP stimulation. Bioinformatic and luciferase reporter analyses identified interleukin-6 receptor (IL-6R) mRNA as a direct target of miR-221-5p in NCM460 cells. Accordingly, SP exposure of NCM460-NK-1R cells increased IL-6R mRNA expression, and overexpression of miR-221-5p reduced IL-6R expression. Nuclear factor κB and c-Jun N-terminal kinase inhibition decreased SP-induced miR-221-5p expression. MiR-221-5p expression was increased in both TNBS- and DSS-induced colitis and in colonic biopsy samples from ulcerative colitis but not Crohn’s disease patients compared with controls. In mice, intracolonic administration of a miR-221-5p chemical inhibitor exacerbated TNBS- and DSS-induced colitis and increased colonic tumor necrosis factor-α, C-X-C motif chemokine 10 (Cxcl10), and collagen, type II, α 1 (Col2α1) mRNA expression. In situ hybridization in TNBS- and DSS-exposed colons revealed increased miR-221-5p expression primarily in colonocytes.ConclusionsOur results reveal a novel NK-1R-miR-221-5p-IL-6R network that protects from colitis. The use of miR-221-5p mimics may be a promising approach for colitis treatment

Lipocalin-2 deficiency attenuates endothelial dysfunction associated with aging and obesity

Conference Theme: Emerging Therapies for an Aging Populatio

Neurotensin—regulated miR-133α is involved in proinflammatory signalling in human colonic epithelial cells and in experimental colitis

ObjectiveNeurotensin (NT) mediates colonic inflammation through its receptor neurotensin receptor 1 (NTR1). NT stimulates miR-133α expression in colonic epithelial cells. We investigated the role of miR-133α in NT-associated colonic inflammation in vitro and in vivo.DesignmiR-133α and aftiphilin (AFTPH) levels were measured by quantitative PCR. Antisense (as)-miR-133α was administrated intracolonicaly prior to induction of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and dextran sodium sulfate (DSS)-induced colitis. The effect of AFTPH was examined by gene silencing in vitro.ResultsNT increased miR-133α levels in NCM-460 overexpressing NTR1 (NCM460-NTR1) and HCT-116 cells. NT-induced p38, ERK1/2, c-Jun, and NF-κB activation, as well as IL-6, IL-8 and IL-1β messenger RNA (mRNA) expression in NCM-460-NTR1 cells were reduced in miR-133α-silenced cells, while overexpression of miR-133α reversed these effects. MiR-133α levels were increased in TNBS (2 day) and DSS (5 day) colitis, while NTR1 deficient DSS-exposed mice had reduced miR-133α levels, compared to wild-type colitic mice. Intracolonic as-miR-133α attenuated several parameters of colitis as well expression of proinflammatory mediators in the colonic mucosa. In silico search coupled with qPCR identified AFTPH as a downstream target of miR-133α, while NT decreased AFTPH expression in NCM-460-NTR1 colonocytes. Gene silencing of AFTPH enhanced NT-induced proinflammatory responses and AFTPH levels were downregulated in experimental colitis. Levels of miR-133α were significantly upregulated, while AFTPH levels were downregulated in colonic biopsies of patients with ulcerative colitis compared to controls.ConclusionsNT-associated colitis and inflammatory signalling are regulated by miR-133α-AFTPH interactions. Targeting of miR-133α or AFTPH may represent a novel therapeutic approach in inflammatory bowel disease

Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the antiaging and metabolic effects of sirtuins

Sirtuins are a family of NAD+-dependent protein deacetylases that regulate cellular functions through deacetylation of a wide range of protein targets. Overexpression of Sir2,the first gene discovered in this family, is able to extend the life span in various organisms. The anti-aging effects of human homologues of sirtuins, SIRT1-7, have also been suggested by animal and human association studies. However, the precise mechanisms whereby sirtuins exert their anti-aging effects remain elusive. In this study, we aim to identify novel interacting partners of SIRT1 and SIRT3, two human sirtuins ubiquitously expressed in many tissue types. Our results demonstrate that SIRT1 and SIRT3 are localized within different intracellular compartments, mainly nuclei and mitochondria, respectively. Using affinity purification and MALDI-TOF/TOF-MS/MS analysis, their potential interacting partners have been identified from the enriched subcellular fractions and specific interactions confirmed by co-immunoprecipitation and Western blotting experiment. Further analyses suggest that overexpression of SIRT1 or SIRT3 in HEK293 cells could induce hypoacetylation and affect the intracellular localizations and protein stabilities of their interacting partners. Taken together, the present study has identified a number of novel SIRT protein interacting partners, which might be critically involved in the anti-aging and metabolic regulatory activities ofsirtuins. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.link_to_subscribed_fulltex

Lipocalin-2, an inflammatory adipokine, uncouples endothelial nitric-oxide synthase and enhances endothelial dysfunction caused by dietary obesity

Focused Conference Group: YI – Young Investigators’ Session: paper no. 2293Endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases. Lipocalin-2 is a pro-inflammatory adipokine. Its circulating concentration positively associates with adiposity, dyslipidemia, hyperglycemia and insulin resistance. Lipocalin-2 deficiency protects mice from developing ageing- and obesity-induced insulin resistance. In the present study, endothelial function of wild type (WT) and lipocalin-2 knockout (Lcn2-KO) mice was compared by measuring isometric tensions in rings of aortae and carotid arteries from dietary obesity-challenged animals. High fat diet feeding for only three weeks significantly impaired endothelium-dependent relaxation (EDR) to insulin in aortae and enhanced endothelium-dependent contraction (EDC) to acetylcholine in carotid arteries. These endothelial dysfunctions were nearly abolished by lipocalin-2 deficiency. Insulin-induced Akt/eNOS phosphorylation was enhanced in aortae of Lcn2-KO mice. The increases in the ratio of eNOS monomers to dimers, and superoxide anion formation were significantly attenuated in mice without lipocalin-2. The level of nitrotyrosine in the total protein and precipitated eNOS of arteries from wide type mice was increased compared with that in Lcn2-KO vessels, despite a similar expression of eNOS protein. The basal and acetylcholine-stimulated superoxide anion production and COX-1 expression were diminished in Lcn2-KO arteries. Replacement with lipocalin-2 in Lcn2-KO mice time-dependently monomerized eNOS in the aorta, increased COX-1 expression levels, and impaired endothelial functions as demonstrated by reduced EDR and enhanced EDC. Lipocalin-2 plays a critical role in the development of obesity-induced endothelial dysfunction through modulation of eNOS activity and oxidative stress.The 16th World Congress on Basic and Clinical Pharmacology (WorldPharma2010), Copenhagen, Denmark, 17-23 July 2010. In Basic & Clinical Pharmacology & Toxicology, 2010, v. 107, suppl. 1, p. 159-16

Endothelium-dependent contractions induced by aging and diet-induced obesity are attenuated in lipocalin-2 deficient mice

AIM: Levels of Lipocalin-2, a pro-inflammatory adipokine, correlates with adiposity, dyslipidemia, hyperglycemia and insulin resistance. The present study evaluates vascular function in mice with deletion of the lipocalin-2 gene (Lcn2-KO). METHODS: Wild type (WT) and Lcn2-KO mice were fed with standard or high fat diet for 3–17 weeks. Intra-arterial blood pressure was measured. Isometric tension was measured in carotid artery rings with or without endothelium. Protein expression was measured by Western blotting. RESULTS: The obesity-induced increase in systolic blood pressure was attenuated in Lcn2-KO mice. In aged or obese WT mice, acetylcholine (ACh)-elicited endothelium-dependent contractions were abolished by the COX-1 selective inhibitor SC560 and the NADH oxidase inhibitor diphenylene iodonium. These contractions were attenuated in Lcn2-KO mice. ACh-stimulated superoxide anion production, COX-1 mRNA and protein expression were decreased in Lcn2-KO arteries. ACh-induced production of prostacyclins (PGI2) was lower in Lcn2-KO preparations. In aged or obese WT mice, PGI2 caused contractions in rings without endothelium but these contractions were reversed to relaxations in Lcn2-KO arteries. CONCLUSIONS: Lipocalin-2 plays an important role in obesity-induced hypertension and endothelial dysfunction through production of superoxide anions and COX-1 expression.The Experimental Biology 2010, Anaheim, CA., 24-28 April 2010. In The FASEB Journal, 2010, v. 24 Meeting abstract suppl., abstract no. 570.

The effectiveness of a tai-chi exercise program on gross motor coordination, negative symptoms and functional disabilities among patients with chronic schizophrenia: a pilot study

Paper Session 34: Complementary and Integrative Medicine Interventions (P34) - Scientific SessionThis journal suppl. contain abstracts of the 2012 SBM Annual MeetingConference Theme: Engaging New Partners and PerspectivesBACKGROUND: Institutionalized patients with schizophrenia often suffer from negative symptoms, motor and functional impairments more serious than their non-institutionalized counterparts. Exercise can help patients improve well-being and psychiatric symptoms. Tai-chi, in particular, emphasizes body relaxation, mental alertness and motor coordination with known benefits to balance, flexibility, and stress relief. PURPOSE: This pilot study aims to explore the potential benefits of Tai-chi on gross motor coordination, negative symptoms and functioning disabilities towards schizophrenia. METHODS: A randomized wait-list control design was adopted for this 12-session (6-week) Wu-style Tai-chi program. 30 participants were randomly allocated to the Tai-chi or control group. The Minnesota Rate of Manipulation Test, Scale for the Assessment of Negative Symptoms and the World Health Organization Disability Assessment Schedule-II were respectively used to measure gross motor coordination, negative symptoms and functional disabilities at baseline, 1 week post-intervention and 6 weeks post-intervention. Analyses were conducted with the Wilcoxon signed ranks test and Mann-Whitney U test. RESULTS: Tai-chi had a protective effect from deterioration in gross motor coordination (Z=-2.28; p=.023) and interpersonal functioning, the latter with sustained effect 6 weeks after the end of the class (Z=-2.56; p=.01). Controls showed marked deterioration in the above areas throughout the study period. CONCLUSION: This pilot study demonstrated encouraging benefits of Tai-chi on promoting movement coordination and alleviating functional disabilities. Tai-chi emphasizes movement rhythm, with possible benefits to motor desynchrony. This form of group exercise also encourages socialization that may support interpersonal functioning. The relative ease of implementation renders it possible to be promoted at other institutional psychiatric services

Mice lacking lipocalin-2 are protected from developing insulin resistance associated with aging and obesity

The Conference abstracts' website is located at http://www.easd.org/index.php?option=com_content&view=article&id=69&Itemid=509Oral Session - OP 06 Inflammation, insulin action and type 2 diabetes: no. 31BACKGROUND AND AIMS: Obesity is characterized as a low-grade inflammation of the adipose tissue and increased circulating concentrations of pro-inflammatory cytokines. The “inflamed” adipose tissue can secrete a large amount of pro-inflammatory adipokines / cytokines that act as mediators for obesity-related metabolic syndrome. Previous studies have shown that the expression and production of lipocalin-2, a pro-inflammatory adipokine, are elevated in obese animal and human subjects. In this study, we aim to evaluate whether lipocalin-2 deficiency can protect the mice from developing systemic ...link_to_OA_fulltex