Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

Association Between Overweight Sarcopenic Population and Acute Vertebral Osteoporotic Compression Fractures in Females: Retrospective, Cross-Sectional Study.

Background: This study aimed to determine whether the prevalence of acute vertebral osteoporotic compression fractures (VOCF) in the elderly population is related to the distribution of muscles and fat in the human body. Methods: Data of acute VOCF and non-VOCF patients presenting at our institution between January 2018 and May 2020 were analyzed. Patients aged 65 years and older, who underwent body composition test and dual-energy X-ray absorptiometry at the same time were enrolled. After applying exclusion criteria, patients were divided into four groups: normal, sarcopenia without obesity, obesity without sarcopenia, and sarcopenic obesity. Body mass index ≥25 kg/m2 was considered obesity, and sarcopenia was defined as skeletal muscle index lower than 7.0 kg/m2 in males and 5.4 kg/m2 in females. The VOCF rate was analyzed between the groups. Discussion: A total of 461 patients were included, of whom 103 were males. Among them, 163 (35.36%) had normal body composition, 151 (32.75%) had sarcopenia without obesity, 110 (23.86%) had obesity without sarcopenia, and 37 (8.03%) had sarcopenic obesity. The sarcopenic obesity group had the highest rate of acute VOCF (37.8%), which was statistically significant. Specifically, females with sarcopenic obesity and sarcopenia without obesity had significantly higher acute VOCF rates compared to those with normal body compositions. Multivariate analysis showed that sarcopenic obesity was significantly associated with acute VOCF rate overall, as well as in females. Conclusion: Sarcopenic obesity is strongly associated with acute VOCF, especially in females, and it could be an essential criterion for the prevention of acute VOCF.

Magnetic Resonance Imaging of Patellofemoral Morphometry Reveals Age and Gender Variations in the Knees of Children and Adolescents.

BACKGROUND: The morphology and alignment of the patellofemoral joint are crucial risk factors for patellar instability, and the incidence of acute primary patellar dislocation is the highest in women in their second decade of life. The purpose of the study was to analyze age and gender variations of the patellofemoral joint using magnetic resonance imaging (MRI). METHODS: A total of 852 patients aged between 4 and 18 years with a history of knee MRI examinations were screened for eligibility and 663 patients (470 males, 193 females) were included. Patients were divided into groups according to age and sex. The age group was divided into five groups (Group 1, 4-6 years; Group 2, 7-9 years; Group 3, 10-12 years; Group 4, 13-15 years; and Group 5, 16-18 years). Three orthopaedic surgeons measured MRI parameters reflecting the patellofemoral morphology (sulcus angle, lateral trochlear inclination, trochlear facet symmetry, and femoral depth) and alignment (tibial tuberosity-trochlear groove distance, percent sulcus location, and percent tibia tuberosity location). RESULTS: Parameters including tibial tuberosity-trochlear groove distance, sulcus angle, percent tibial tuberosity location, trochlear facet symmetry, and femoral depth showed significant differences between the age groups (p < 0.05). The sulcus angle decreased fin Group 2, and the femoral depth showed an increasing trend with aging in male patients. However, the sulcus angle in females decreased first and then increased in Group 3 as the inflection point. The femoral depth showed an opposite pattern. CONCLUSIONS: Patellofemoral morphometry showed age and gender variation. Notably, the sulcus angle and femoral depth were significantly different between males and females and changed according to the development. These findings may reflect the sex difference and peak incidence of the patellar instability risk. Understanding the morphological changes and differences of the patellofemoral joint may facilitate the diagnosis of patellofemoral pathologies.

Low serum vitamin B12 levels are associated with degenerative rotator cuff tear.

BACKGROUND: Vitamin B12 (Vit B12) deficiency results in elevated homocysteine levels and interference with collagen cross-linking, which may affect tendon integrity. The purpose of this study was to investigate whether serum Vit B12 levels were correlated with degenerative rotator cuff (RC) tear. METHODS: Eighty-seven consecutive patients with or without degenerative RC tear were enrolled as study participants. Possible risk factors (age, sex, medical history, bone mineral density, and serum chemistries including glucose, magnesium, calcium, phosphorus, zinc, homocysteine, Vitamin D, Vit B12, homocysteine, and folate) were assessed. Significant variables were selected based on the results of univariate analyses, and a logistic regression model (backward elimination) was constructed to predict the presence of degenerative RC tear. RESULTS: In the univariate analysis, the group of patients with degenerative RC tear had a mean concentration of 528.4 pg/mL Vit B12, which was significantly lower than the healthy control group (627.1 pg/mL). Logistic regression analysis using Vit B12 as an independent variable revealed that Vit B12 concentrations were significantly correlated with degenerative RC tear (p = 0.044). However, Vit B12 levels were not associated with tear size. CONCLUSION: Low serum levels of Vit B12 were independently related to degenerative RC tear. Further investigations are warranted to determine if Vit B12 supplementation can decrease the risk of this condition.

Cell density-dependent differential proliferation of neural stem cells on omnidirectional nanopore-arrayed surface.

Recently, the importance of surface nanotopography in the determination of stem cell fate and behavior has been revealed. In the current study, we generated polystyrene cell-culture dishes with an omnidirectional nanopore arrayed surface (ONAS) (diameter: 200 nm, depth: 500 nm, center-to-center distance: 500 nm) and investigated the effects of nanotopography on rat neural stem cells (NSCs). NSCs cultured on ONAS proliferated better than those on the flat surface when cell density was low and showed less spontaneous differentiation during proliferation in the presence of mitogens. Interestingly, NSCs cultured on ONAS at clonal density demonstrated a propensity to generate neurospheres, whereas those on the flat surface migrated out, proliferated as individuals, and spread out to attach to the surface. However, the differential patterns of proliferation were cell density-dependent since the distinct phenomena were lost when cell density was increased. ONAS modulated cytoskeletal reorganization and inhibited formation of focal adhesion, which is generally observed in NSCs grown on flat surfaces. ONAS appeared to reinforce NSC-NSC interaction, restricted individual cell migration and prohibited NSC attachment to the nanopore surface. These data demonstrate that ONAS maintains NSCs as undifferentiated while retaining multipotency and is a better topography for culturing low density NSCs.

Discovery of a Small Molecule that Enhances Astrocytogenesis by Activation of STAT3, SMAD1/5/8, and ERK1/2 via Induction of Cytokines in Neural Stem Cells.

Identification of small molecules that direct neural stem cells (NSCs) into specific cell types would be helpful to understand the molecular mechanisms involved in regulation of NSC fate, and facilitate the development of therapeutic applications. In the current study, we developed and screened small molecules that can modulate the fate of NSCs that are derived from rat fetal cortex. Among these compounds, compounds 5 and 6 successfully differentiated NSCs into astrocytes and neurons, respectively. Compound 5 induced astrocytogenesis by increasing expression of interleukin-6, bone morphogenetic protein 2 and leukemia inhibitory factor and through consequent phosphorylation of signal transducer and activator of transcription 3 and Sma- and Mad-related protein 1/5/8 in NSCs. In addition, compound 5 increased the expression of fibroblast growth factor (FGF) 2 and FGF8 which may regulate the branching and morphology of astrocytes. Taken together, our results suggest that these small molecules can serve as a useful tool to study cell fate determination in NSCs and be used as an inexpensive alternative to cytokines to study mechanisms of astrocytogenesis.

An Aminopropyl Carbazole Derivative Induces Neurogenesis by Increasing Final Cell Division in Neural Stem Cells.

P7C3 and its derivatives, 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(p-tolylamino)propan-2-ol (1) and N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)-4-methylbenzenesulfonamide (2), were previously reported to increase neurogenesis in rat neural stem cells (NSCs). Although P7C3 is known to increase neurogenesis by protecting newborn neurons, it is not known whether its derivatives also have protective effects to increase neurogenesis. In the current study, we examined how 1 induces neurogenesis. The treatment of 1 in NSCs increased numbers of cells in the absence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), while not affecting those in the presence of growth factors. Compound 1 did not induce astrocytogenesis during NSC differentiation. 5-Bromo-2'-deoxyuridine (BrdU) pulsing experiments showed that 1 significantly enhanced BrdU-positive neurons. Taken together, our data suggest that 1 promotes neurogenesis by the induction of final cell division during NSC differentiation.

A correction method using a support vector machine to minimize hematocrit interference in blood glucose measurements.

Point-of-care testing glucose meters are widely used, important tools for determining the blood glucose levels of people with diabetes, patients in intensive care units, pregnant women, and newborn infants. However, a number of studies have concluded that a change in hematocrit (Hct) levels can seriously affect the accuracy of glucose measurements. The aim of this study was to develop an algorithm for glucose calculation with improved accuracy using the Hct compensation method that minimizes the effects of Hct on glucose measurements. The glucose concentrations in this study were calculated with an adaptive calibration curve using linear fitting prediction and a support vector machine, which minimized the bias in the glucose concentrations caused by the Hct interference. This was followed by an evaluation of performance according to the international organization for standardization (ISO) 15197:2013 based on bias with respect to the reference method, the coefficient of variation, and the valid blood samples/total blood samples within the ±20% and 15% error grids. Chronoamperometry was performed to verify the effect of Hct variation and to compare the proposed method. As a result, the average coefficients of variation for chronoamperometry and the Hct compensation method were 2.43% and 3.71%, respectively, while the average biases (%) for these methods were 12.08% and 5.69%, respectively. The results of chronoamperometry demonstrated that a decrease in Hct levels increases glucose concentrations, whereas an increase in Hct levels reduces glucose concentrations. Finally, the proposed method has improved the accuracy of glucose measurements compared to existing chronoamperometry methods.

Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis.

Development of a cardiorespiratory monitoring system based on pressure change of aircushion.

Heartbeat and respiration are fundamental vital signs used for estimation of patient's status. In this study, we have proposed a simple method to monitor the heartbeat and respiration based on displacements of human body which occur due to periodic heartbeat and breathing.

Unconstrained respiration and heart rate monitoring system based on a PPG pillow during sleep.

In this paper, we have suggested a novel method to monitor respiration and heart rate using a PPG pillow during sleep. The proposed method employs a pillow containing a reflective type PPG sensor and a simple extraction algorithm. The PPG pillow was placed under the back of a neck to acquire PPG signal on the assumption that the subjects hardly change their position. The results showed considerable coincidence between the extracted respiratory rhythm and the reference signal in case of either a medium or a high respiration speed, while it was hard to extract the rhythm based on the trace line formed by linear interpolating the detected valleys under the condition of a low respiration speed. HRV could be alternative to the interpolated trace line in the case. This study shows the proposed method has an advantage of processing simplicity so as to be used easily in unconstrained respiration and heart rate monitoring.