CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1.

Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson\u27s disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1(-/-) mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP(+))-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP(+)-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP(+)-induced neurotoxicity by blocking ASK1-mediated signaling

A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells

Abstract Background Mesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells. Methods Tonsil-derived mesenchymal stem cells (TMSCs) with 20–25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses. Results The culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-β-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p < 0.001). We also found that culture-aged TMSCs had decreased expressions of integrin α3 (ITGA3) and phosphorylated AKT protein (p-AKT-Ser473) compared to the control TMSCs. Conclusions Our data suggest that activation of ECM-receptor signaling, specifically involved with integrin family-mediated activation of the intracellular cell survival-signaling molecule AKT, can regulate stem cell senescence in TMSCs. Among these identified factors, ITGA3 was found to be a representative biomarker of the senescent TMSCs. Exclusion of the TMSCs with the senescent TMSC markers in this study could potentially increase the therapeutic efficacy of TMSCs in clinical applications

FedTherapist: Mental Health Monitoring with User-Generated Linguistic Expressions on Smartphones via Federated Learning

Psychiatrists diagnose mental disorders via the linguistic use of patients. Still, due to data privacy, existing passive mental health monitoring systems use alternative features such as activity, app usage, and location via mobile devices. We propose FedTherapist, a mobile mental health monitoring system that utilizes continuous speech and keyboard input in a privacy-preserving way via federated learning. We explore multiple model designs by comparing their performance and overhead for FedTherapist to overcome the complex nature of on-device language model training on smartphones. We further propose a Context-Aware Language Learning (CALL) methodology to effectively utilize smartphones' large and noisy text for mental health signal sensing. Our IRB-approved evaluation of the prediction of self-reported depression, stress, anxiety, and mood from 46 participants shows higher accuracy of FedTherapist compared with the performance with non-language features, achieving 0.15 AUROC improvement and 8.21% MAE reduction.Comment: Accepted to the 2023 Conference on Empirical Methods in Natural Language Processing (EMNLP 2023

Association between shift work and obesity among female nurses: Korean Nurses’ Survey

Background: Shift work has been hypothesized as a risk factor for obesity. In this study, we investigated the association between current shift work and body mass index (BMI) among female nurses in Korea. The relationship between duration of shift work and BMI of the participants was also evaluated. Methods: This cross-sectional survey evaluated participants in the Korean Nurses’ Survey, conducted from October to December 2011, using web-based self-administered questionnaires. A total of 9,989 nurses were included among 10,000 who registered on the survey web site (5,287 shift workers and 4,702 non-shift workers). Current shift workers were divided into tertiles of shift work duration (0.08–3.00 years, n = 1,732; 3.08–6.75 years, n = 1,731; and 6.83–38.00 years, n = 1,686). The BMI thresholds of overweight and obesity were ≥23 kg/m2 and ≥25 kg/m2, respectively. Data were analyzed using SPSS software. Results: Mean participant age was 33.2 ± 8.6 years and the mean BMI was 20.9 ± 2.5 kg/m2. There were statistically significant differences in current smoking status, regular drinking habit, dietary habits, regular exercise, sleep problems and self-perceived health status according to duration of shift work. The overall prevalence of overweight/obesity (18.6%) and obesity (7.4%) increased significantly as shift work duration increased from the lowest to highest tertile (P for trend <0.001). Multivariate logistic regression analysis revealed no association between current shift work and BMI. However, after adjusting for potential confounders, the participants with the longest duration of shift work were 1.63 (95% CI, 1.22–2.17) times more likely to be overweight or obese than those with the shortest duration. There was a significant positive association between obesity and shift work duration in the unadjusted analysis; however, it was attenuated and no longer significant in the multivariate model. Conclusions: The duration of shift work was positively associated with prevalence of overweight/obesity in nurses in Korea. Although these findings need to be confirmed in prospective studies, they suggest that special attention should be paid to female nurses with a long duration of shift work

Progression from Chronic Atrophic Gastritis to Gastric Cancer; Tangle, Toggle, Tackle with Korea Red Ginseng

Key molecular players that link inflammation to carcinogenesis are prostaglandins, cytokines, nuclear factor-κB (NF-κB), chemokines, angiogenic growth factors, and free radicals, all of which lead to increased mutations and altered functions of important enzymes and proteins, for example, activation of oncogenic products and/or inhibition of tumor suppressor proteins, in inflamed tissues, thus contributing to multi-stage carcinogenesis process. Interpreted reversely, the identification of the molecular mechanisms by which chronic inflammation increases cancer risk or optimal intervention of targeted drugs or agents during the inflammation-associated carcinogenic process could be a necessary basis for developing new strategy of cancer prevention at many sites. In this review, we discuss the possibilities for cancer prevention by controlling inflammation process in Helicobacter pylori (H. pylori)-associated inflamed stomach with Korea red ginseng. Korea red ginseng is a good example of a natural herb that has ubiquitous properties that are conductive to stop inflammatory carcinogenesis that is un wanted outcome of H. pylori infection, rendering rejuvenation of chronic atrophic gastritis

A multicenter, prospective, randomized, controlled trial evaluating the safety and efficacy of intracoronary cell infusion mobilized with granulocyte colony-stimulating factor and darbepoetin after acute myocardial infarction: study design and rationale of the 'MAGIC cell-5-combination cytokine trial'

<p>Abstract</p> <p>Background</p> <p>Bone marrow derived stem/progenitor cell transplantation after acute myocardial infarction is safe and effective for improving left ventricular systolic function. However, the improvement of left ventricular systolic function is limited. This study will evaluate novel stem/progenitor cell therapy with combination cytokine treatment of the long-acting erythropoietin analogue, darbepoetin, and granulocyte colony-stimulating factor (G-CSF) in patients with acute myocardial infarction.</p> <p>Methods</p> <p>The 'MAGIC Cell-5-Combination Cytokine Trial' is a multicenter, prospective, randomized, 3-arm, controlled trial with blind evaluation of the endpoints. A total of 116 patients will randomly receive one of the following three treatments: an intravenous darbepoetin infusion and intracoronary infusion of peripheral blood stem cells mobilized with G-CSF (n = 58), an intracoronary infusion of peripheral blood stem cells mobilized with G-CSF alone (n = 29), or conventional therapy (n = 29) at phase I. Patients with left ventricular ejection fraction < 45% at 6 months, in the patients who received stem cell therapy at phase I, will receive repeated cell therapy at phase II. The objectives of this study are to evaluate the safety and efficacy of combination cytokine therapy with erythropoietin and G-CSF (phase I) and repeated progenitor/stem cell treatment (phase II).</p> <p>Discussion</p> <p>This is the first study to evaluate the safety and efficacy of combination cytokine based progenitor/stem cell treatment.</p> <p>Trial registration</p> <p><url>http://www.ClinicalTrials.gov</url> identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00501917">NCT00501917</a>.</p