TRAIL and DcR1 Expressions Are Differentially Regulated in the Pancreatic Islets of STZ- versus CY-Applied NOD Mice

TNF-related apoptosis-inducing ligand (TRAIL) is an important component of the immune system. Although it is well acknowledged that it also has an important role in Type 1 Diabetes (T1D) development, this presumed role has not yet been clearly revealed. Streptozotocin (STZ) and Cyclophosphamide (CY) are frequently used agents for establishment or acceleration of T1D disease in experimental models, including the non-obese diabetic (NOD) mice. Although such disease models are very suitable for diabetes research, different expression patterns for various T1D-related molecules may be expected, depending on the action mechanism of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY and analyzed the expression profiles of TRAIL ligand and receptors throughout disease development. TRAIL ligand expression followed a completely different pattern in STZ- versus CY-accelerated disease, displaying a prominent increase in the former, while appearing at reduced levels in the latter. Decoy receptor 1 (DcR1) expression also increased significantly in the pancreatic islets in STZ-induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions may be part of a defensive strategy of the beta islets against the infiltrating leukocytes, while the immune-suppressive agent CY may partly hold down this defense, contributing further to diabetes development

Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions

Nonobese Diabetic (NOD) mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR) mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ). STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

Humbling Turkishness: Undoing the Strategies of Exclusion and Inclusion of Turkish Modernity

Kurds make up about a fifth of Turkey's population. Turkey has taken steps – albeit slowly and reluctantly – towards increased recognition of Kurdish cultural and linguistic rights. However, within Turkey there is also a steeply rising tide of Turkish nationalism, prejudice and intolerance towards Kurds, and increasing anti‐Kurdish sentiment. This article brings studies of Kurdishness and Turkishness into a single conversation and traces the relationship between Turkish modernity, Orientalized Kurdishness and the construction of Turkishness as the efendi (master) identity. It does this by drawing attention to “strategies of exclusion and inclusion” in the construction of official Turkish history, and relates these to the way in which the tense borders between Kurds and Turks are maintained and currently reproduced. It also presents a normative argument in favour of “humbling Turkishness” and “solidarity trading zones

Comparing the Working Memory Capacity with Cognitive Flexibility, Cognitive Emotion Regulation, and Learning Styles of University Students: A Domain General View

Introduction: The goal of this study was to investigate the relationship of working memory capacity with the use of cognitive emotion regulation strategies, cognitive flexibility level, and learning styles of university students. Methods: In the present study (N = 39), the participants completed the Emotion Regulation Questionnaire, Cognitive Flexibility Scale, Kolb Learning Styles Inventory, and Vermunt Learning Styles Inventory and three WM capacity (WMC) tasks that are Rotation Span Task, Operation Span Task, and Symmetry Span Task. Their WMCs were assessed, and the relationship of it was compared with cognitive emotion regulation, cognitive flexibility, and learning styles. Results: The results indicated that there is a significant difference and negative correlation (r= −0.341) between Operation Span Task and refocus on planning. Findings of the research indicated correlations between emotion regulation strategies and between cognitive flexibility and two emotion regulation strategies that are refocus on planning (r = 0.528) and positive reappraisal (r = 0.574). Only one learning style that is Processing Strategies in Vermunt Learning Style Inventory was found significantly different in terms of the cognitive flexibility level of the participants. The results also indicated a positive correlation between verbal and spatial WM tasks which support the domain general view for WMC. Conclusions: Further studies are advised to be conducted between cognitive emotion regulation strategies and working memory capacity as these findings may have significant implications for understanding the correlation between memory and emotion