Cumulative effect of unemployment on suicide mortality in South Korean workers (2018-2019).

BACKGROUND: While unemployment is known to increase the risk of suicide, its cumulative effect remains underexplored. This study investigates how unemployment affects suicide mortality and whether the effect varies based on the number of unemployment spells using two years of nationwide data. METHODS: Using the data from the National Statistical Office and Employment Insurance Database for 2018 and 2019, we identified an average of 2365 cases of suicide over two years among 7.76 million workers aged 25-64 years who had been employed within one year before their suicide. The number of unemployment spells was counted using the employment history of the past five years. We calculated crude suicide mortality rates per 100 000 population, age- and sex- standardized mortality rates (SMRs), and proportionate mortality rates (PMRs) for suicide. RESULTS: Over the two years, the crude suicide rate was 30.0 per 100 000 among the general population and 30.5 among workers. Workers with no unemployment spells in the past five years had a significantly lower SMR (0.44; 0.42-0.46), while those with four or more unemployment spells had a significantly higher SMR (3.13; 2.92-3.35) than the general population. These findings were consistent across all sex and age groups. Additionally, workers with four or more unemployment spells had a significantly higher PMR than the general population. CONCLUSION: The impact of unemployment on suicide mortality intensifies as the number of unemployment spells increases. These results underscore the necessity for additional social and psychological support along with economic assistance for individuals facing recurrent unemployment.

Microbiomic association between the saliva and salivary stone in patients with sialolithiasis.

Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.

The association of tonsillar microbiota with biochemical indices based on obesity and tonsillar hypertrophy in children.

The correlation between tonsil microbiome and tonsillar hypertrophy has not been well established. Given that oral dysbiosis is related to several metabolic diseases and that tonsillar hypertrophy leads to disordered breathing during sleep and obesity in children, it is necessary to investigate the relationship between the oral microbiome and tonsillar hypertrophy. After 16S rRNA amplicon sequencing of tonsillectomy samples, we evaluated the correlation between the tonsil microbiome and biochemical blood indices in pediatric patients who underwent tonsillectomy. Groups are classified into two categories: based on BMI, and grades 2, 3, and 4 based on tonsil size. Children with obesity and tonsillar hypertrophy have similar microbiome compositions and induce comparable changes in microbiome abundance and composition, confirming the association from a metagenomic perspective. In addition, obesity and tonsillar hypertrophy demonstrated a strong correlation with the Proteobacteria to Firmicutes (P/F) ratio, and among various biochemical indicators, alanine aminotransferase (ALT) levels increase with obesity and tonsillar hypertrophy, indicating a possible association of tonsil microbiome and liver metabolism. These novel findings demonstrate the significance of the tonsil microbiome and suggest the need for tonsil regulation, particularly during childhood.

Nitrosylation of ß2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of ß2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-ß2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-ß2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION: This is the first discovery of a new target molecule of NO, ß2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-ß2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Application of tree-based machine learning classification methods to detect signals of fluoroquinolones using the Korea Adverse Event Reporting System (KAERS) database.

BACKGROUND: Safety issues for fluoroquinolones have been provided by regulatory agencies. This study was conducted to identify signals of fluoroquinolones reported in the Korea Adverse Event Reporting System (KAERS) using tree-based machine learning (ML) methods. RESEARCH DESIGN AND METHODS: All adverse events (AEs) associated with the target drugs reported in the KAERS from 2013 to 2017 were matched with drug label information. A dataset containing label-positive and -negative AEs was arbitrarily divided into training and test sets. Decision tree, random forest (RF), bagging, and gradient boosting machine (GBM) were fitted on the training set with hyperparameters tuned using five-fold cross-validation and applied to the test set. The ML method with the highest area under the curve (AUC) scores was selected as the final ML model. RESULTS: Bagging was selected as the final ML model for gemifloxacin (AUC score: 1) and levofloxacin (AUC: 0.9987). RF was selected in ciprofloxacin, moxifloxacin, and ofloxacin (AUC scores: 0.9859, 0.9974, and 0.9999 respectively). We found that the final ML methods detected additional signals that were not detected using the disproportionality analysis (DPA) methods. CONCLUSIONS: The bagging-or-RF-based ML methods performed better than DPA and detected novel AE signals previously unidentified using the DPA methods.

Preditores de maus-tratos ao idoso relacionados a idosos e a seus cuidadores primários / Predictores de malos tratos a personas mayores relacionados con las personas mayores y sus cuidadores principales / Predictors for elder mistreatment related to older adults and their primary caregivers

Resumo Objetivos Identificar fatores preditivos de maus-tratos ao idoso relacionados a idosos e seus principais cuidadores e a relação entre formação profissional de saúde e identificação de maus-tratos. Métodos Estudo quantitativo e analítico. Os potenciais fatores de risco para maus-tratos relacionados a 40 idosos e seus cuidadores foram coletados por meio da observação de 12 profissionais de saúde e em uma associação de enfermeiras visitantes. O treinamento de profissionais de saúde na identificação de maus-tratos foi investigado. Estatística descritiva, teste exato de Fisher e análise de regressão linear múltipla foram usados para investigar as relações entre a ocorrência de maus-tratos ao idoso e fatores de risco relacionados ao idoso e ao cuidador, e os fatores preditivos para maus-tratos ao idoso. Resultados A dependência dos idosos em relação aos cuidadores e as condições crônicas de saúde dos cuidadores principais foram preditores de maus-tratos ao idoso. Os fatores de risco apresentados pelos cuidadores primários tendiam a afetar mais os maus-tratos ao idoso do que a dependência dos idosos. O número de treinamentos em maus-tratos ao idoso realizado pelos participantes, seu conhecimento sobre quem é responsável por notificar os maus-tratos ao idoso, o tipo de cuidador principal dos idosos e a condição crônica de saúde dos cuidadores foram os fatores correlacionados que afetaram os maus-tratos ao idoso. Conclusão As descrições de maus-tratos ao idoso das vítimas e perpetradores são difíceis de avaliar; portanto, recomenda-se a triagem mais ampla sob perspectiva dos profissionais de saúde. Futuras pesquisas de enfermagem devem explorar intervenções indiretas, como manipular os fatores de risco que os cuidadores primários representam, a fim de diminuir a ocorrência de maus-tratos ao idoso. Estudos futuros testando modelos de previsão de trajetória dentro de uma amostra maior e mais controlada devem ser conduzidos.

Resumen Objetivos Identificar factores predictivos de malos tratos a personas mayores relacionados con las personas mayores y sus cuidadores principales y la relación entre la formación profesional en salud y la identificación de malos tratos. Métodos Estudio cuantitativo y analítico. Los factores potenciales de riesgo de malos tratos relacionados con 40 personas mayores y sus cuidadores fueron recopilados mediante la observación de 12 profesionales de la salud y en una asociación de enfermeras visitantes. Se investigó la capacitación de profesionales de la salud en la identificación de malos tratos. Se utilizó la estadística descriptiva, la prueba exacta de Fisher y el análisis de regresión lineal múltiple para investigar las relaciones entre los casos de malos tratos a personas mayores y los factores de riesgo relacionados con personas mayores y su cuidador, y los factores predictivos de malos tratos a personas mayores. Resultados La dependencia de personas mayores con relación a los cuidadores y las condiciones crónicas de salud de los cuidadores principales fueron predictores de malos tratos a personas mayores. Los factores de riesgo presentados por los cuidadores principales tendían a afectar más los malos tratos a personas mayores que la dependencia de las personas mayores. El número de capacitaciones en malos tratos a personas mayores realizado por quienes participaron, sus conocimientos sobre quién es responsable de notificar los malos tratos a personas mayores, el tipo de cuidador principal de personas mayores y la condición crónica de salud de los cuidadores fueron los factores correlacionados que afectaron los malos tratos a personas mayores. Conclusión Las descripciones de malos tratos a personas mayores por parte de las víctimas y perpetradores son difíciles de evaluar; por lo tanto, se recomienda un triaje más amplio bajo la perspectiva de profesionales de la salud. Futuros estudios de enfermería deben investigar intervenciones indirectas, como manipular los factores de riesgo que los cuidadores principales representan, a fin de reducir los casos de malos tratos a personas mayores. Deben realizarse estudios futuros probando modelos de previsión de trayectoria dentro de una muestra más grande y más controlada.

Abstract Objectives To identify predictive factors for elder mistreatment (EM) related to older adults and their primary caregivers and the relationship between healthcare professional training and identification of EM. Methods This was a quantitative and analytic study. Potential risk factors for EM related to 40 older adults and their caregivers were collected through observation by 12 healthcare professionals and in a visiting nurses association. Training of healthcare professionals on EM identification was investigated. Descriptive statistics, Fisher's exact test, and multilevel regression analysis were used to investigate the relationships between the occurrence of EM and older adults and caregiver-related risk factors, and the predictive factors for EM. Results The older adults' dependency on caregivers and primary caregivers' chronic health conditions predicted EM. The risk factors the primary caregivers posed tended to affect EM more than the dependency older adults posed. The number of EM training the participants attended, their knowledge of who is responsible for reporting EM, the type of older adults' primary caregivers, and caregivers' chronic health condition were the correlating factors affecting EM. Conclusion Victims' and perpetrators' descriptions of EM are difficult to gauge; therefore, the broader screening of healthcare professionals' views is recommended. Future nursing research should explore indirect interventions, such as manipulating the risk factors primary caregivers pose, to decrease the occurrence of EM. A subsequent study testing Path prediction models within a bigger and more controlled sample are also warranted.

Cyclin-Dependent Kinase 1 Inhibition Potentiates the Proliferation of Tonsil-Derived Mesenchymal Stem Cells by Delaying Cellular Senescence.

Mesenchymal stem cells (MSCs) have been widely used in tissue regeneration and stem cell therapy and are currently being tested in numerous clinical trials. Senescence-related changes in MSC properties have attracted considerable attention. Senescent MSCs exhibit a compromised potential for proliferation; senescence acts as a stress response that prevents the proliferation of dysfunctional cells by inducing an irreversible cell cycle arrest. Here, we established a senescent MSC model using senescence-associated ß-galactosidase, proliferation, and cell cycle assays. We further identified novel biomarker candidates for old, senescent tonsil-derived MSCs (TMSCs) using transcriptomics. A plot of the cellular senescence pathway showed cyclin-dependent kinase 1 (CDK1; +8-fold) and CDK2 (+2-fold), and transforming growth factor beta 2 (TGFB2; +2-fold) showed significantly higher expression in old TMSCs than in young TMSCs. The CDK family was shown to be related to cell cycle and proliferation, as confirmed by quantitative RT-PCR. As replicative senescence of TMSCs, the gene and protein expression of CDK1 was significantly increased, which was further validated by inhibiting CDK1 using an inhibitor and siRNA. Taken together, we suggest that the CDK1 can be used as a selective senescence biomarker of MSCs and broaden the research criteria for senescent mechanisms.

Validation of the Patient Health Questionnaire-9 for Screening Depressive Disorders among Korean Employees: A Longitudinal Study of the National Health Examination Data.

This nationwide longitudinal study examined the screening utility of the Patient Health Questionnaire-9 (PHQ-9) for Korean workers (aged 20, 30, 40, 50, 60, and 70 years) who completed the questionnaire in 2018. Data on disease names and health-related behaviors were collected from the National Health Insurance Service (NHIS). Follow-up began on 1 January 2018, and the primary endpoint was the hospitalization date for depression, self-harm, or suicide or 31 December 2019. Of the 766,351 participants, 741,423 received depression screening. Those screened were classified into normal (n = 716,760) and high-risk groups (n = 24,663) based on PHQ-9 scores. The incidence of hospital admissions for depression, self-harm, or suicide in the non-screened, normal, and high-risk groups was analyzed, and the PHQ-9's validity was examined. There were more females in the high-risk group than in the normal group, and the income distribution differed. The two-year cumulative incidence was highest for the high-risk group (4.21%), followed by the normal (0.89%) and non-screened groups (0.80%). The PHQ-9's sensitivity was low (males: 14.2%; females: 13.8%). Its specificity for males and females was 97.1% and 96.3%, respectively. Our findings may help develop a system to prevent suicides and hospitalizations attributed to workplace depression.

Optimization of skeletal muscle-derived fibroblast isolation and purification without the preplating method.

Most embryonic fibroblasts have been widely used as feeder cells to support stem cell cultures, and in the case of human embryonic stem cells, the manipulation with human embryonic stem cells is prohibited in most countries for ethical reasons. However, the importance of tissue origin is increasing because cell surface markers and extracellular matrix proteins are secreted differently depending on the tissue origin of fibroblasts. In particular, as fibroblasts and myoblasts are mixed in skeletal muscle tissue, it is necessary to selectively separate only fibroblasts. The preplating technique was used to isolate fibroblasts from mouse skeletal muscle tissue, and the morphological and functional characteristics were investigated to optimize the efficient purification method of isolated fibroblasts. Cell morphology and doubling time were not notably associated with preplating. The preplating method did not induce significant functional changes, including those in the expression of fibroblast-specific genes (Vim and Fsp1) and myoblast-specific genes (Myod and Myog), until passage number 5. Moreover, skeletal muscle-derived fibroblasts before and after cryopreservation retained the morphological and functional properties until passage 5 after thawing. Based on the comprehensive results, the characteristics of skeletal muscle-derived fibroblasts were maintained up to passage 5 regardless of preplating, and fibroblast-specific properties were maintained even after cryopreservation. In this study, we optimized the isolation and purification methods for skeletal muscle-derived fibroblasts. These methods are expected to be used in various applications for tissue engineering.

Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78.

Controlling the senescence of mesenchymal stem cells (MSCs) is essential for improving the efficacy of MSC-based therapies. Here, a model of MSC senescence was established by replicative subculture in tonsil-derived MSCs (TMSCs) using senescence-associated ß-galactosidase, telomere-length related genes, stemness, and mitochondrial metabolism. Using transcriptomic and proteomic analyses, we identified glucose-regulated protein 78 (GRP78) as a unique MSC senescence marker. With increasing cell passage number, GRP78 gradually translocated from the cell surface and cytosol to the (peri)nuclear region of TMSCs. A gelatin-based hydrogel releasing a sustained, low level of reactive oxygen species (ROS-hydrogel) was used to improve TMSC quiescence and self-renewal. TMSCs expressing cell surface-specific GRP78 (csGRP78+), collected by magnetic sorting, showed better stem cell function and higher mitochondrial metabolism than unsorted cells. Implantation of csGRP78+ cells embedded in ROS-hydrogel in rats with calvarial defects resulted in increased bone regeneration. Thus, csGRP78 is a promising biomarker of senescent TMSCs, and the combined use of csGRP78+ cells and ROS-hydrogel improved the regenerative capacity of TMSCs by regulating GRP78 translocation.

Cell-Permeable Oct4 Gene Delivery Enhances Stem Cell-like Properties of Mouse Embryonic Fibroblasts.

Direct conversion of one cell type into another is a trans-differentiation process. Recent advances in fibroblast research revealed that epithelial cells can give rise to fibroblasts by epithelial-mesenchymal transition. Conversely, fibroblasts can also give rise to epithelia by undergoing a mesenchymal to epithelial transition. To elicit stem cell-like properties in fibroblasts, the Oct4 transcription factor acts as a master transcriptional regulator for reprogramming somatic cells. Notably, the production of gene complexes with cell-permeable peptides, such as low-molecular-weight protamine (LMWP), was proposed to induce reprogramming without cytotoxicity and genomic mutation. We designed a complex with non-cytotoxic LMWP to prevent the degradation of Oct4 and revealed that the positively charged cell-permeable LMWP helped condense the size of the Oct4-LMWP complexes (1:5 N:P ratio). When the Oct4-LMWP complex was delivered into mouse embryonic fibroblasts (MEFs), stemness-related gene expression increased while fibroblast intrinsic properties decreased. We believe that the Oct4-LMWP complex developed in this study can be used to reprogram terminally differentiated somatic cells or convert them into stem cell-like cells without risk of cell death, improving the stemness level and stability of existing direct conversion techniques.

Quantitative CT image-based structural and functional changes during asthma acute exacerbations.

Asthma acute exacerbations (AE) have been investigated using quantitative computed tomography (QCT)-based imaging metrics, but QCT has not yet been used to investigate a comprehensive set of imaging metrics during AE. This study aims to explore imaging features, captured both at segmental and parenchymal scales, during asthma AE compared with those in stable asthma (SA). Two sets of the QCT images at total lung capacity (TLC) and functional residual capacity (FRC) were captured for 14 subjects during asthma AE and in SA phase, respectively. We calculated airway wall thickness (WT), hydraulic diameter (Dh), and airway circularity (Cr) of the 36 segmental airways; percentage of functional small airway disease (fSAD%); percentage of emphysema; tissue fraction (ßtiss); and coefficient of variation of ßtiss (CV of ßtiss). We performed Spearman correlation tests for changes in QCT metrics and pulmonary function tests, measured in AE and SA. During asthma AE, structural metrics, that is, WT, Dh, and Cr, were not changed significantly. In functional metrics, CV of ßtiss at FRC indicating the heterogeneity of lung tissue distribution was significantly increased, whereas the mean of ßtiss at FRC did not change during AE. An increase of fSAD% during AE was most correlated with a decrease of forced expiratory volume in 1 s and forced vital capacity, especially in the lower lobes. This study demonstrates that the heterogeneous feature of ßtiss measured at lower lobes is more noticeable during asthma AE, compared with other traditional imaging metrics. This metric could be utilized to identify unique features during asthma AE.NEW & NOTEWORTHY Using two sets of inspiration and expiration images, the difference of segmental airway structure and parenchymal lung function is assessed by comparing the QCT images during asthma acute exacerbations with those in stable asthma. This study also introduces a useful application of an imaging-based metric, estimating the heterogeneity of tissue distribution. This could be a phenotype for the asthma acute exacerbation.

Octanoyl glycol chitosan enhances the proliferation and differentiation of tonsil-derived mesenchymal stem cells.

Biofunctional polymers have been widely used to enhance the proliferation and functionality of stem cells. Here, we report the development of a new biofunctional polymer, octanoyl glycol chitosan (OGC), and demonstrate its effects on the cell cycle and stem cell function using tonsil-derived mesenchymal stem cells (TMSCs). OGC treatment (100 µg/mL) significantly increased the proliferation of TMSCs, which could be attributed to cyclin D1 up-regulation in the G1 phase of the cell cycle. Additionally, OGC enhanced the ability of TMSCs to differentiate into adipocytes, chondrocytes, and osteoblasts. Taken together, this new biofunctional polymer, OGC, can promote stemness and osteogenesis, as well as induce stem cell proliferation by enhancing the intracellular metabolic rate and regulating the cell cycle. Thus, in the future, OGC could be a potential therapeutic additive for improving stem cell function.

Association between the microbiomes of tonsil and saliva samples isolated from pediatric patients subjected to tonsillectomy for the treatment of tonsillar hyperplasia.

Oral microbes have the capacity to spread throughout the gastrointestinal system and are strongly associated with multiple diseases. Given that tonsils are located between the oral cavity and the laryngopharynx at the gateway of the alimentary and respiratory tracts, tonsillar tissue may also be affected by microbiota from both the oral cavity (saliva) and the alimentary tract. Here, we analyzed the distribution and association of the microbial communities in the saliva and tonsils of Korean children subjected to tonsillectomy because of tonsil hyperplasia (n = 29). The microbiome profiles of saliva and tonsils were established via 16S rRNA gene sequencing. Based on the alpha diversity indices, the microbial communities of the two groups showed high similarities. According to Spearman's ranking correlation analysis, the distribution of Treponema, the causative bacterium of periodontitis, in saliva and tonsils was found to have a significant positive correlation. Two representative microbes, Prevotella in saliva and Alloprevotella in tonsils, were negatively correlated, while Treponema 2 showed a strong positive correlation between saliva and tonsils. Taken together, strong similarities in the microbial communities of the tonsils and saliva are evident in terms of diversity and composition. The saliva microbiome is expected to significantly affect the tonsil microbiome. Furthermore, we suggest that our study creates an opportunity for tonsillar microbiome research to facilitate the development of novel microbiome-based therapeutic strategies.

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

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)-ß-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.

Effects of scan body exposure and operator on the accuracy of image matching of implant impressions with scan bodies.

STATEMENT OF PROBLEM: Accurate image matching of the scan with the design of the scan body is essential to replicate the actual implant position in the software program. In situations where the scan part of the scan body is partially embedded in the gingival tissue, the influence of the scan image deficiency on the accuracy of image matching has not been clarified. PURPOSE: The purpose of this in vitro study was to examine the effects of scan body exposure and different operators on the accuracy of image matching of the scan body. MATERIAL AND METHODS: Six groups with different scan body exposures (fully exposed, 0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm less exposed) were digitized, and the scan images were transferred to a CAD software program, where the design of the scan body was matched to the scan image of each group. Based on the position of the scan body design, a virtual implant was created. The image matching process was performed 7 times for each group by 2 operators (N=84). The linear and angular deviations of the virtual implants were analyzed 3-dimensionally. Two-way ANOVA, equivalence, and concordance correlation coefficient statistics were used to verify the effects of scan body exposure and operator on the image matching. RESULTS: As the exposure of the scan body was reduced, the deviations in implant positioning were significantly increased (P<.001). The concordance correlation coefficient indicated strong agreement between the 2 operators. CONCLUSIONS: Reduced exposure of the scan body significantly influenced the accuracy of implant positioning in the software program. Operator differences may not affect the accuracy of scan body image matching.

A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis.

We report dual therapeutic effects of a synthetic heparin-binding peptide (HBP) corresponding to residues 15-24 of the heparin binding site in BMP4 in a collagen-induced rheumatic arthritis model (CIA) for the first time. The cell penetrating capacity of HBP led to improved cartilage recovery and anti-inflammatory effects via down-regulation of the iNOS-IFNγ-IL6 signaling pathway in inflamed RAW264.7 cells. Both arthritis and paw swelling scores were significantly improved following HBP injection into CIA model mice. Anti-rheumatic effects were accelerated upon combined treatment with Enbrel® and HBP. Serum IFNγ and IL6 concentrations were markedly reduced following intraperitoneal HBP injection in CIA mice. The anti-rheumatic effects of HBP in mice were similar to those of Enbrel®. Furthermore, the combination of Enbrel® and HBP induced similar anti-rheumatic and anti-inflammatory effects as Enbrel®. We further investigated the effect of HBP on damaged chondrocytes in CIA mice. Regenerative capacity of HBP was confirmed based on increased expression of chondrocyte biomarker genes, including aggrecan, collagen type II and TNFα, in adult human knee chondrocytes. These findings collectively support the utility of our cell-permeable bifunctional HBP with anti-inflammatory and chondrogenic properties as a potential source of therapeutic agents for degenerative inflammatory diseases.

Quantitative CT-based structural alterations of segmental airways in cement dust-exposed subjects.

BACKGROUND: Dust exposure has been reported as a risk factor of pulmonary disease, leading to alterations of segmental airways and parenchymal lungs. This study aims to investigate alterations of quantitative computed tomography (QCT)-based airway structural and functional metrics due to cement-dust exposure. METHODS: To reduce confounding factors, subjects with normal spirometry without fibrosis, asthma and pneumonia histories were only selected, and a propensity score matching was applied to match age, sex, height, smoking status, and pack-years. Thus, from a larger data set (N = 609), only 41 cement dust-exposed subjects were compared with 164 non-cement dust-exposed subjects. QCT imaging metrics of airway hydraulic diameter (Dh), wall thickness (WT), and bifurcation angle (θ) were extracted at total lung capacity (TLC) and functional residual capacity (FRC), along with their deformation ratios between TLC and FRC. RESULTS: In TLC scan, dust-exposed subjects showed a decrease of Dh (airway narrowing) especially at lower-lobes (p < 0.05), an increase of WT (wall thickening) at all segmental airways (p < 0.05), and an alteration of θ at most of the central airways (p < 0.001) compared with non-dust-exposed subjects. Furthermore, dust-exposed subjects had smaller deformation ratios of WT at the segmental airways (p < 0.05) and θ at the right main bronchi and left main bronchi (p < 0.01), indicating airway stiffness. CONCLUSIONS: Dust-exposed subjects with normal spirometry demonstrated airway narrowing at lower-lobes, wall thickening at all segmental airways, a different bifurcation angle at central airways, and a loss of airway wall elasticity at lower-lobes. The airway structural alterations may indicate different airway pathophysiology due to cement dusts.

l-Citrulline restores nitric oxide level and cellular uptake at the brain capillary endothelial cell line (TR-BBB cells) with glutamate cytotoxicity.

OBJECTIVE: Glutamate excitotoxicity provokes neuronal cell damage and death, leading to collapse of the blood-brain barrier (BBB). Recently, it has been reported that l-citrulline, a neutral amino acid and a major precursor of l-arginine in the nitric oxide (NO) cycle, can prevent both neuronal cell death and cerebrovascular cell loss in brain ischemia. Therefore, the objective of this study was to investigate the effect of l-citrulline on glutamate cytotoxicity in the BBB using the conditionally immortalized rat brain capillary endothelial cell line (TR-BBB cells) as an in vitro model of the BBB. METHODS: Cell viability was determined using MTT assay. Cellular uptake of [14C] l-citrulline and expression levels of rat large neutral amino acid transporter 1 (rLAT1), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) at mRNA level were performed using quantitative real-time polymerase chain reaction (PCR) analysis. NO production from TR-BBB cells was measured using Griess reagents. All experiments were performed after treatment of TR-BBB cells with glutamate alone or co-treatment with l-citrulline, l-arginine, and/or taurine for 24 h. RESULTS: l-Citrulline treatment increased cell viability, [14C] l-citrulline uptake, and the mRNA levels of LAT1 and eNOS in TR-BBB cells treated with glutamate. However, iNOS mRNA expression was inhibited by l-citrulline. NO production and transcript level of iNOS were markedly increased by glutamate treatment alone. However, co-treatment with l-citrulline, taurine, or both l-citrulline and taurine decreased NO levels and mRNA levels of iNOS in TR-BBB cells treated with glutamate. In co-treatment of TR-BBB cells with l-arginine, a NO donor, and glutamate, NO levels were increased and expression levels of iNOS mRNA were similar compared to those in cells treated with glutamate alone. CONCLUSION: l-Citrulline can restore NO level and its cellular uptake in TR-BBB cells with glutamate cytotoxicity. Supplying l-citrulline at the BBB may provide neuroprotective effect to improve cerebrovascular dysfunction such as a brain ischemia.