Predictors of cognitive performance in bipolar disorder: The role of educational degree and inflammatory markers
JOURNAL OF PSYCHIATRIC RESEARCH
Authors: Barbosa, Izabela Guimaraes; Ferreira, Rodrigo de Almeida; Rocha, Natalia Pessoa; Mol, Giovana Carvalho; Chiaccjio Leite, Flavia da Mata; Bauer, Isabelle E.; Teixeira, Antonio L.
Abstract
Background: The aim of this article was to evaluate the cognitive status of remitted patients with bipolar disorder (BD) using Mini-Mental State Examination (MMSE), Frontal Assessment Battery, and Brief Assessment of Cognition in Affective Disorders (BAC-A). The BAC-A is a comprehensive test battery addressing the cognitive domains compromised in BD. We also aimed to analyze potential clinical and immune predictors of cognitive performance in BD. Methods: Remitted patients with BD (M +/- S.E: 43.80 +/- 10.87 years) and age-matched controls (M +/- S.E: 43.52 +/- 11.72) were administered clinical questionnaires and cognitive tests. Inflammatory plasma levels (IL-2, IL-4, IL-6, IL-10, IFN-gamma, TNF alpha, IL-17A, sTNFR1, and sTNFR2) were measured using an enzyme-linked immunosorbent assay. We generated a global cognitive performance index based on BAC-A scores. Multivariate analyses compared cognitive and immune measures across groups. A regression analysis was performed to examine the relationship between global cognitive performance, clinical and immune parameters in BD. Results: Remitted patients with BD performed poorly on tasks of affective processing, verbal memory, working verbal memory, and executive functioning. Patients with BD presented higher plasma levels sTNFR1, TNF alpha, IFN, IL2, IL4, IL6, IL10, and IL17compared with controls. Education and MMSE were found to be positively correlated with global cognitive performance. IL6 plasma levels were negatively correlated with global cognitive performance. Conclusion: The major determinants of poor cognitive performance in BD were education and IL6 plasma levels.
Epigallocatechin-3-gallate protects Wharton's jelly derived mesenchymal stem cells against in vitro heat stress
EUROPEAN JOURNAL OF PHARMACOLOGY
Authors: Butt, Hira; Mehmood, Azra; Ejaz, Asim; Humayun, Shamsa; Riazuddin, Sheikh
Abstract
The deteriorating effects of heat stress abrogate the therapeutic implications of human Wharton's jelly derived mesenchymal stem cells (hWJMSCs) transplanted in burn wounds. Topically applied green tea extract comprising epigallocatechin-3-gallate (EGCG) is known to repair burn wounds. Here, we investigated the protective role of EGCG priming of hWJMSCs against heat-induced stress in vitro along with the involved underlying mechanism. EGCG ameliorated heat-induced injuries as demonstrated by significantly improved cell morphology, viability, triggered cell migration and enhanced expression of heat shock proteins. In addition, decreased lactate dehydrogenase release and reduced percentage of senescent and apoptotic cells were observed. EGCG priming alleviated the detrimental effects of thermal stress in hWJMSCs as observed by significant down-regulation in expression of BCL2 associated X (BAX), interleukin 6 (IL6), and interleukin 1 beta (IL1 beta) genes, while proliferating cell nuclear antigen (PCNA), BCL2 like 1 (BCL2L1), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF beta 1), hepatocyte growth factor (HGF) and interleukin 4 (IL4) genes were up-regulated. Accompanying gene expression data, EGCG primed cells exposed to heat stress also exhibited remarkably increased secretion of VEGF, HGF, epidermal growth factor (EGF), stromal-derived factor 1 (SDF1) proteins while the reduced release of IL-6, and tumor necrosis factor-alpha (TNF-alpha) proteins. Further, synergistic activation of extracellular-signal-regulated kinase (ERK) and protein kinase B (PKB/AKT) proteins was observed. These findings suggest that EGCG priming might enhance the therapeutic efficacy of hWJMSCs in the burnt tissue through regulation of ERK and AKT signaling pathways, and improved cellular responses.