Plasma pentraxin-3 levels and its role in childhood obesity-Is it anti-inflammatory? A matched group study.

OBJECTIVE: Obesity has been associated with chronic low-grade systemic inflammation. This study aimed to investigate the relationship of pentraxin-3 (PTX-3) with anthropometric measurements, dietary content and physical activity level in children. DESIGN: A matched group study. PATIENTS: This study was conducted with 91 children aged 6-17 years, divided into two groups: "non-obese group" (Body Mass Index Standard Deviation Score [BMI SDS] <95th percentile) and "obese group" (BMI SDS ≥95th percentile). MEASUREMENTS: Plasma PTX-3 levels. RESULTS: The mean age of 91 children included in the study was 12.34 ± 2.86 years. Plasma PTX-3 levels were significantly higher in obese children (p = .028). No significant correlation was found between BMI SDS and plasma PTX-3 values, but a weak positive correlation was found when physical activity level was controlled (r = .176, p = .049). In addition, it was found that fat mass was a partial mediator of plasma PTX-3 level, and an increase in the amount of subcutaneous adipose tissue negatively affected plasma PTX-3 level. Plasma PTX-3 level showed a weak positive correlation (r = .223, p = .017) with physical activity score and dietary polyunsaturated fatty acid intake, while a weak negative correlation with neutrophil-to-lymphocyte ratio. One unit increase in physical activity score or polyunsaturated fatty acid level caused 0.730 and 2.061 unit increases in plasma PTX-3 level, respectively; while one unit increase in dietary fat intake caused 0.413-unit decrease. CONCLUSION: There was an indirect relationship between the amount of subcutaneous adipose tissue and PTX-3 level. The results of our study suggested that plasma PTX-3 was associated with lower levels of inflammation in children.

The Common Point of Countries Successful Policies in the Struggle Against COVID-19: Women Leaders.

During the COVID-19 pandemic, which is one of the biggest epidemics of the last century and can be regarded as a global tragedy, leaders had to mobilize many resources of their countries quickly and persuade their citizens to change their routine behavior. The approach followed by the leaders of the country in their efforts to convince their people has been an important factor in their success or failure. This paper aims to examine with Michel Foucault's notion of biopower, and discourses and behaviors of women leaders in countries against the global pandemic which cost high life tool gave harsh messages to the humanity. For this purpose, leadership examples in Finland, Iceland, Taiwan and New Zealand will be examined in detail using the discourse analysis technique. As a result, in current times when populist and autocratic leader style is on the rise, women leaders not only took their countries to success, but they also managed to inspire other countries. More importantly, the struggle of women leaders against the pandemic revealed that a different management style is possible.

The paracaspase MALT1 is a downstream target of Smad3 and potentiates the crosstalk between TGF-ß and NF-kB signaling pathways in cancer cells.

TGF-ß signaling mediates its biological effects by engaging canonical Smad proteins and crosstalking extensively with other signaling networks, including the NF-kB pathway. The paracaspase MALT1 is an intracellular signaling molecule essential for NF-kB activation downstream of several key cell surface receptors. Despite intensive research on TGF-ß and NF-kB interactions, the significance of MALT1 in this context remains undecoded. Here we provide experimental evidence supporting that MALT1 functions to converge these pathways. Using A549 and Huh7 cancer cell line models, we report that TGF-ß stimulation enhances MALT1 protein and transcript levels in a time- and dose-dependent manner. Systematic and selective perturbation of TGF-ß signaling components identifies MALT1 as a downstream target of Smad3. Rescue experiments in SMAD3 knockout cells confirm that C-terminal phosphorylation of Smad3 is central to MALT1 induction. Corroborating these data, we document that the expression of SMAD3 and MALT1 genes are positively correlated in TCGA cohorts, and we trace the molecular basis of MALT1 elevation to promoter activation. Functional studies in parental as well as NF-kB p65 signaling reporter engineered cells conclusively reveal that MALT1 is paramount for TGF-ß-stimulated nuclear translocation and transcriptional activation of NF-kB p65. Furthermore, we find that BCL10 is also implicated in TGF-ß activation of NF-kB target genes, potentially coupling the TGF-ß-MALT1-NF-kB signaling axis to the CARMA-BCL10-MALT1 (CBM) signalosome. The novel findings of this study indicate that MALT1 is a downstream target of the canonical TGF-ß/Smad3 pathway and plays a critical role in modulating TGF-ß and NF-kB crosstalk in cancer.

Opinions of Teachers on Distance Education Applications in English Language Teaching Policies in Northern Cyprus During the COVID-19 Pandemic.

The COVID-19 pandemic affected education institutions just like several other sectors. These institutions, which are among the places where people are found collectively, were the first places that were closed for precaution. Some problems of distance education conducted in online platforms which were assumed upon the termination of face-to-face education emerged in time. Especially in this urgent solution, where the workload of teachers has increased, some application difficulties have been identified in foreign language teaching. From this point of view, considering the foreign language education policy and planning, this study deals with the distance education practices of English teachers, the difficulties they encounter in the process, and their solution proposals. The research, which was designed as a qualitative study, was conducted with a case study design. The participants of the research are 13 English teachers working at the secondary school level in different districts of Northern Cyprus determined by the homogeneous sampling method. The data were collected through semi-structured interviews developed by the researchers. The qualitative data were analyzed with descriptive analysis. As a result of the interviews with the teachers, it has been determined that there are problems related to technology, students, online classes, and planning in English teaching carried out with distance education applications. Accordingly, the teachers offered their recommendations that could be a solution to the existing problems.

The Bright and the Dark Side of TGF-ß Signaling in Hepatocellular Carcinoma: Mechanisms, Dysregulation, and Therapeutic Implications.

Hepatocellular carcinoma (HCC) is associated with genetic and nongenetic aberrations that impact multiple genes and pathways, including the frequently dysregulated transforming growth factor ß (TGF-ß) signaling pathway. The regulatory cytokine TGF-ß and its signaling effectors govern a broad spectrum of spatiotemporally regulated molecular and cellular responses, yet paradoxically have dual and opposing roles in HCC progression. In the early stages of tumorigenesis, TGF-ß signaling enforces profound tumor-suppressive effects, primarily by inducing cell cycle arrest, cellular senescence, autophagy, and apoptosis. However, as the tumor advances in malignant progression, TGF-ß functionally switches to a pro-tumorigenic signal, eliciting aggressive tumor traits, such as epithelial-mesenchymal transition, tumor microenvironment remodeling, and immune evasion of cancer cells. On this account, the inhibition of TGF-ß signaling is recognized as a promising therapeutic strategy for advanced HCC. In this review, we evaluate the functions and mechanisms of TGF-ß signaling and relate its complex and pleiotropic biology to HCC pathophysiology, attempting to provide a detailed perspective on the molecular determinants underlying its functional diversion. We also address the therapeutic implications of the dichotomous nature of TGF-ß signaling and highlight the rationale for targeting this pathway for HCC treatment, alone or in combination with other agents.

Systematic Analysis of Cytostatic TGF-Beta Response in Mesenchymal-Like Hepatocellular Carcinoma Cell Lines.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most challenging malignancies, with high morbidity and mortality rates. The transforming growth factor-ß (TGF-ß) pathway plays a dual role in HCC, acting as both tumor suppressor and promoter. A thorough understanding of the mechanisms underlying its opposing functions is important. The growth suppressive effects of TGF-ß remain largely unknown for mesenchymal HCC cells. Using a systematic approach, here we assess the cytostatic TGF-ß responses and intracellular transduction of the canonical TGF-ß/Smad signaling cascade in mesenchymal-like HCC cell lines. METHODS: Nine mesenchymal-like HCC cell lines, including SNU182, SNU387, SNU398, SNU423, SNU449, SNU475, Mahlavu, Focus, and Sk-Hep1, were used in this study. The cytostatic effects of TGF-ß were evaluated by cell cycle analysis, BrdU labeling, and SA-ß-Gal assay. RT-PCR and western blot analysis were utilized to determine the mRNA and protein expression levels of TGF-ß signaling components and cytostatic genes. Immunoperoxidase staining and luciferase reporter assays were performed to comprehend the transduction of the canonical TGF-ß pathway. RESULTS: We report that mesenchymal-like HCC cell lines are resistant to TGF-ß-induced growth suppression. The vast majority of cell lines have an active canonical signaling from the cell membrane to the nucleus. Three cell lines had lost the expression of cytostatic effector genes. CONCLUSION: Our findings reveal that cytostatic TGF-ß responses have been selectively lost in mesenchymal-like HCC cell lines. Notably, their lack of responsiveness was not associated with a widespread impairment of TGF-ß signaling cascade. These cell lines may serve as valuable models for studying the molecular mechanisms underlying the loss of TGF-ß-mediated cytostasis during hepatocarcinogenesis.