Contribution of Osteoblast and Osteoclast Supernatants to Bone Formation: Determination Using a Novel Microfluidic Chip.

We fabricated a microfluidic chip (osteoblast [OB]-osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of different supernatant distributions on osteogenesis or osteoclastogenesis. Computer-aided design was used to produce an OB-OC chip from polydimethylsiloxane. A pressure controller was assembled and different blends of OB and OC supernatants were correctly determined. OB and OC supernatants were placed on the upper panels of the OB-OC chip after differentiation for an in vitro evaluation. We then tested the changes in osteogenesis using MC3T3-E1 cells in the middle chambers. We observed that a 75:25 distribution of OB and OC supernatants was the most potent in osteogenesis. We then primed the osteogenic differentiation of MC3T3-E1 cells using an OB-OC mixed supernatant or an OB supernatant alone (supernatant ratios of 75:25 or 100:0, respectively). These cells were placed on the calvarial defect sites of rats. Microcomputed tomography and histological analyses determined a significantly higher bone formation in the group exposed to the OB-OC supernatant at a ratio of 75:25. In this study, we demonstrate the applicability of an OB-OC chip to evaluate the effect of different supernatant distributions of OB and OC. We observed that the highest bone-forming potential was in MC3T3-E1 cells treated with conditioned media, specifically the OB-OC supernatant at a ratio of 75:25.

Ultrasound-guided selective supraclavicular nerve block for postoperative pain control in children receiving Hickman catheter or chemoport insertion: A randomized controlled trial.

BACKGROUND: Optimal pain management after insertion of a central venous catheter in children remains unclear. AIM: This study aimed to evaluate the effects of a selective supraclavicular nerve block on postoperative analgesia in pediatric patients undergoing hickman catheter or chemoport insertion. METHODS: Fifty patients aged 3-18 years scheduled for elective Hickman or chemoport insertion were randomized into two groups of 25 each: one group received an ultrasound-guided selective supraclavicular nerve block with 0.1 mL/kg of 0.5% ropivacaine (SSCNB group), and the other group did not receive a nerve block (control group). The primary outcome was the postoperative Wong-Baker Faces Pain Rating Scale score measured between 10 and 30 min after surgery. Secondary outcomes included pain scores at 1, 3, and 24 h after the surgery, block-related complications, length of stay in the postanesthesia care unit, postoperative analgesic consumption, and time to first analgesic use 24 h after surgery. RESULTS: The worst pain score within 30 min in the recovery room was significantly lower in the SSCNB group compared to the control group (6 [5-7] vs. 3 [2-4]; median difference, -3; 95% CI, -4 to -1; p < .001). Pain scores at 1, 3, and 24 h after surgery were also significantly lower in the SSCNB group. The need for both opioid and non-opioid analgesics in the postoperative period was significantly lower in the SSCNB group (36.0% vs. 0%; p = .002 and 44.0% vs. 16.0%; mean difference, -28%; 95% CI, -56 to 0.19; p = .033, respectively), while other secondary outcomes were not significantly different between the two groups. CONCLUSIONS: Ultrasound-guided SSCNB is an effective method for managing postoperative pain in children undergoing Hickman catheter or chemoport insertion, reducing the need for analgesics within 24 h after surgery.

Driving pressure-guided ventilation and postoperative pulmonary complications in thoracic surgery: a multicentre randomised clinical trial.

BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.

Ultrasound-guided esophageal compression during mask ventilation in small children: a prospective observational study.

BACKGROUND: The use of cricoid compression to prevent insufflation remains controversial, and its use in children is limited. This study aimed to examine the effect of real-time ultrasound-guided esophageal compression on the prevention of gastric insufflation. METHOD: This prospective observational study was conducted with fifty children aged < 2 years undergoing general anesthesia. Patients were excluded if they were at an increased risk for gastric regurgitation or pulmonary aspiration. Following anesthetic induction under spontaneous breathing, ultrasound-guided esophageal compression was performed during pressure-controlled face-mask ventilation using a gradual increase in peak inspiratory pressure from 10 to 24 cm H2O to determine the pressure at which gastric insufflation occurred. The primary outcome was the incidence of gastric insufflation during anesthetic induction with variable peak inspiratory pressure after real-time ultrasound-guided esophageal compression was applied. RESULTS: Data from a total of 42 patients were analyzed. Gastric insufflation was observed in 2 (4.7%) patients. All patients except one had their esophagus on the left side of the trachea. Applying ultrasound-guided esophageal compression did not affect the percentage of glottic opening scores (P = 0.220). CONCLUSIONS: The use of real-time ultrasound-guided esophageal compression pressure can aid preventing gastric insufflation during face-mask ventilation in children less than 2 years old. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04645043.

Performance time of anesthesiology trainees for cricothyroid membrane identification and characteristics of cricothyroid membrane in pediatric patients using ultrasonography.

BACKGROUND: Identifying the cricothyroid membrane is an essential technical skill for front-of-neck access procedures. AIMS: This study evaluated the usefulness of cricothyroid membrane identification in pediatric patients using ultrasonography by anesthesiology trainees without experience in airway ultrasound and collected anatomical data on the cricothyroid membrane and its surrounding airway structures in children. METHODS: This prospective observational study included children aged <18 years scheduled to undergo general anesthesia and anesthesiology trainees who identified the cricothyroid membrane in five sequential anesthetized patients using ultrasonography. A pediatric anesthesiologist confirmed the accuracy of the identified cricothyroid membrane and recorded the performance time. The primary aims were the cricothyroid membrane identification success rate and performance time. The secondary aims were the characterization of the cricothyroid membrane and its surrounding structures. RESULTS: Overall, 150 pediatric patients and 30 anesthesiology trainees were analyzed. The cricothyroid membrane identification success rate using ultrasonography was 100% in all the attempts using a transverse approach. The mean (standard deviation) performance time was 27.2 (18.6) s and 31.0 (23.8) s using the transverse and longitudinal approaches, respectively. The performance time decreased by 3.1 (p = .003, 95% confidence interval [CI] = -5.1--1.0) and 5.2 (p = .007, 95% CI = -8.9--1.4) seconds per increase in number of attempts with the transverse and longitudinal approaches, respectively. The cricothyroid membrane length was mostly correlated with the patients' height (r = .75, p < .001), and the blood vessels surrounding the cricothyroid membrane were observed in 95.9% of the patients. CONCLUSIONS: Anesthesiology trainees without experience in airway ultrasound successfully identified the cricothyroid membrane in pediatric patients using ultrasonography after a brief training period. Further research is required as the identification of a structure does not predict the success of the actual procedure, particularly if done in an emergency situation.

The effect of dexmedetomidine on neuroprotection in pediatric cardiac surgery patients: study protocol for a prospective randomized controlled trial.

BACKGROUND: Infants undergoing cardiac surgery under cardiopulmonary bypass are vulnerable to postoperative neurodevelopmental delays. Dexmedetomidine has been shown to have protective effects on the heart, kidneys, and brain in animals and adults undergoing cardiac surgery with cardiopulmonary bypass. We hypothesized that dexmedetomidine would have a neuroprotective effect on infants undergoing cardiopulmonary bypass and planned a prospective randomized controlled trial with postoperative neurodevelopment measurements. METHODS: This is a single-center, prospective, double-blinded, randomized controlled trial with 1:1 allocation. A cohort of 160 infants undergoing cardiac surgery with cardiopulmonary bypass will be enrolled. After induction, dexmedetomidine will be infused with a loading dose of 1 µg/kg and a maintenance dose of 0.5 µg/kg/h or the same amount of normal saline will be administered. Upon initiation of cardiopulmonary bypass, an additional dose of dexmedetomidine (0.01 µg/cardiopulmonary priming volume) will be mixed with the cardiopulmonary bypass circuit. The primary outcome will be the proportion of infants who score lower than 85 in any of the cognitive, language, or motor Bayley scales of infant development-III tests 1 year after the surgery. Other feasible outcome measures will include differences in plasma glial fibrillary acidic protein, troponin I, interleukin-6, urinary neutrophil gelatinase-associated lipocalin, and perioperative major adverse events. The results of the Bayley scales of infant development-III test from the study group and the control group will be compared using a chi-squared test under intention-to-treat analysis. A generalized estimating equation will be used to analyze repeated measurements over time. DISCUSSION: This study will enable us to assess whether the use of dexmedetomidine can alter the early neurodevelopmental outcome in infants undergoing cardiac surgery with cardiopulmonary bypass and also estimate effects of dexmedetomidine on other organs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484922. Registered on 24 July 2020.

Gene Network Analysis for Osteoporosis, Sarcopenia, Diabetes, and Obesity in Human Mesenchymal Stromal Cells.

The systemic gene interactions that occur during osteoporosis and their underlying mechanisms remain to be determined. To this end, mesenchymal stromal cells (MSCs) were analyzed from bone marrow samples collected from healthy individuals (n = 5) and patients with osteoporosis (n = 5). A total of 120 osteoporosis-related genes were identified using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) software. In order to analyze these genes, we constructed a heatmap of one-way hierarchical clustering and grouped the gene expression patterns of the samples. The MSCs from one control participant showed a similar expression pattern to that observed in the MSCs of three patients with osteoporosis, suggesting that the differentiating genes might be important genetic determinants of osteoporosis. Then, we selected the top 38 genes based on fold change and expression, excluding osteoporosis-related genes from the control participant. We identified a network among the top 38 genes related to osteoblast and osteoclast differentiation, bone remodeling, osteoporosis, and sarcopenia using the Molecule Activity Predictor program. Among them, 25 genes were essential systemic genes involved in osteoporosis. Furthermore, we identified 24 genes also associated with diabetes and obesity, among which 10 genes were involved in a network related to bone and energy metabolism. The study findings may have implications for the treatment and prevention of osteoporosis.

Validation of the Masimo O3™ regional oximetry device in pediatric patients undergoing cardiac surgery.

We assessed the accuracy of Masimo O3™ regional cerebral oxygen saturation (rSO2) readings by comparing them with reference values and evaluated the relationship between rSO2 and somatic tissue oxygen saturation (StO2) in children undergoing cardiac surgery. After anesthesia induction, pediatric sensors were applied to the forehead and foot sole, and rSO2 and StO2 values were monitored continuously. Before cardiopulmonary bypass (CPB), FIO2 was set to 0.2, 0.5, and 0.8 serially every 15 min. After CPB, FIO2 was reversed. The reference values (SavO2) were calculated by combining arterial (SaO2) and central venous oxygen saturation (SvO2) readings from the arterial and central lines, respectively (0.7 [Formula: see text] SvO2 + 0.3 [Formula: see text] SaO2). In total, 265 pairs of rSO2/StO2 and SavO2 from 49 patients were analyzed. The bias, standard deviation (SD), standard error (SE), and root mean squared error (RMSE) of rSO2 were 2.6%, 4.5%, 0.3%, and 4.3%, respectively. The limits of agreement ranged from -6.3% to 11.6%. Trend accuracy analysis yielded a relative mean error of -1.4%, with an SD of 4.3%, SE of 0.2%, and RMSE of 3.9%. According to multiple linear regression analysis, the application of CPB, FIO2, Hb level, and tip location of the central venous catheter influenced the bias (all P < 0.05). Furthermore, the correlation between rSO2 and StO2 was weak (r = 0.254). rSO2 readings by the Masimo O3™ device and pediatric sensor had good absolute and trending accuracies with respect to the calculated reference values in children undergoing cardiac surgery. rSO2 and StO2 cannot be used interchangeably.Clinical trial registration http://clinicaltrials.gov (number: NCT04208906).

Therapeutic Potential of Human Fetal Mesenchymal Stem Cells in Musculoskeletal Disorders: A Narrative Review.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta.

Central venous catheter-related thrombosis in pediatric surgical patients: A prospective observational study.

BACKGROUND: Perioperative central venous catheters are required but may be associated with various complications. AIMS: The purpose of our study was to assess the incidence and perioperative risk factors for catheter-related internal jugular vein thrombosis in pediatric surgical patients. METHODS: This prospective observational study included children under 6 years of age who were scheduled to undergo central venous catheterization of the right internal jugular vein under general anesthesia. A central venous catheter was inserted under real-time ultrasound guidance. An investigator examined for thrombosis using ultrasonography at predetermined time points. The primary aim was the incidence of catheter-related thrombosis from insertion until the 5th day postoperatively or the removal of the central venous catheter. The secondary aim was the determination of the risk factors for thrombosis. RESULTS: Eighty patients completed the study. Internal jugular vein thrombi were found in 31 patients (38.8%, 95% CI 28.0-49.4). On multiple logistic regression analyses, the number of insertion attempts was the only influencing factor for catheter-related thrombosis (p < .001). More than two insertion attempts increased the risk of thrombosis (odds ratio 5.6; 95% CI 1.7 - 18.7, p = .004). Anesthesia time (p = .017; mean difference 166.4 min; 95% CI 55.7-277.1), intraoperative red blood cell transfusion (p = .001; median difference 21.1 ml kg-1 ; 95% CI 6.6-34.4), and intensive care unit stay (p = .001; median difference 100.0 h; 95% CI 48-311) differed between patients with transient thrombosis and those with thrombosis lasting for more than 3 days. CONCLUSION: Internal jugular vein thrombosis was frequently detected by ultrasound following central venous catheterization in pediatric surgical patients. Multiple insertion attempts may be associated with the incidence of thrombosis. The clinical relevance of thrombi detected via ultrasound surveillance has not been determined.

Author Correction: Transcription Factor HOXA9 is Linked to the Calcification and Invasion of Papillary Thyroid Carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Seroconversion of red blood cell antibody in ABO-incompatible living donor liver transplantation -a case report.

BACKGROUND: Liver transplantation usually requires blood transfusion, and a red blood cell (RBC) antibody screen is essential for the prevention of a hemolytic reaction. Since proper ABO-compatible grafts are lacking, ABO-incompatible living donor liver transplantation (ABO-i LDLT) with desensitization is a feasible therapy. Desensitization includes intravenous rituximab injection and plasmapheresis before surgery. CASE: A 60-year-old female was diagnosed with hepatitis B virus-related hepatocellular carcinoma and planned for ABO-i LDLT. She tested positive in a RBC antibody screen over two years; however, she tested negative for the test after desensitization. Clinicians noted the seroconversion during induction, and thus, a delay in the preparation of adequate packed RBC was unavoidable. CONCLUSIONS: Even when the latest RBC antibody screen is negative after immunosuppression, clinicians should consider the possibility of a prior positive result to promote safer medical treatment and management.

Transcription Factor HOXA9 is Linked to the Calcification and Invasion of Papillary Thyroid Carcinoma.

Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the RUNX2 promoter. We found that RUNX2 promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and in vitro tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.

STRA6 as a possible candidate gene for pathogenesis of osteoporosis from RNA­seq analysis of human mesenchymal stem cells.

To identify novel candidate genes associated with osteoporosis, RNA­sequence analysis of human mesenchymal stem cells (hMSCs) from patients with osteoporosis (G3) and osteopenia (G2), and healthy controls (G1) was performed. Differentially expressed genes (DEGs) from among the three groups were identified. DEGs were separated into nine groups according to their gene expression patterns: UU (up and up), UF (up and flat), UD (up and down), FU (flat and up), FF (flat and flat), FD (flat and down), DU (down and up), DF (down and flat), and DD (down and down). Among the 42 DEGs between G3 and G1, eight candidate genes, namely stimulated by retinoic acid 6 (STRA6), melanophilin, neurotrophic receptor tyrosine kinase 2, cartilage oligomeric matrix protein, collagen type XI α 1 chain, integrin subunit ß 2, monooxygenase DBH­like 1 and selenoprotein P, were selected, as they demonstrated consistent gene expression patterns of UU, FU, FD, and DD. Among these eight genes, STRA6 was highly expressed in the osteoporosis group and based on additional data from quantitative polymerase chain reaction analysis, it was selected for further study. In order to investigate whether STRA6 served a functional role in osteoblast or adipocyte differentiation, the effects of STRA6 expression changes in pluripotent stem cell C3H10T1/2, preosteoblast MC3T3­E1 and stromal ST2 cell lines were examined. Bone morphogenetic protein 2 enhanced STRA6 expression only at the early stage of osteoblast differe-ntiation, and overexpression of STRA6 temporally inhibited the expression of osteoblastogenesis markers, including runt related transcription factor 2, bone sialoprotein and osteocalcin. Furthermore, the knockdown of STRA6 slightly enhanced nodule formation at the late stage of osteoblast differentiation, and overexpression of STRA6 in ST2 cells enhanced adipocyte differentiation. Taken together, STRA6 expression could be associated with the pathogenesis of osteoporosis by promoting adipocyte differentiation over osteoblast differentiation in the hMSC population.

Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis.

Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis. Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteogenesis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p=0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p=0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and obesity.

Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra.

Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records.

GATA4 negatively regulates bone sialoprotein expression in osteoblasts.

GATA4 has been reported to act as a negative regulator in osteoblast differentiation by inhibiting the Dlx5 transactivation of Runx2 via the attenuation of the binding ability of Dlx5 to the Runx2 promoter region. Here, we determine the role of GATA4 in the regulation of bone sialoprotein (Bsp) in osteoblasts. We observed that the overexpression of Runx2 or Sox9 induced the Bsp expression in osteoblastic cells. Silencing GATA4 further enhanced the Runx2- and Sox9-mediated Bsp promoter activity, whereas GATA4 overexpression down-regulated Bsp promoter activity mediated by Runx2 and Sox9. GATA4 also interacted with Runx2 and Sox9, by attenuating the binding ability of Runx2 and Sox9 to the Bsp promoter region. Our data suggest that GATA4 acts as a negative regulator of Bsp expression in osteoblasts. [BMB Reports 2016; 49(6): 343-348].

GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2.

Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteogenic conditioned cell culture system. In addition, overexpression of GATA4 attenuated expression of osteogenic marker genes, including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of which are important for osteoblast differentiation and function. Overexpression of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that GATA4 acts as a negative regulator in osteoblast differentiation by downregulation of Runx2.

The Association between Oxidative Stress and Metabolic Syndrome in Adults.

BACKGROUND: In this Study, we investigated the effects of lifestyle and metabolic syndrome on free oxygen radical levels in men and women in Korea. METHODS: A total of 254 adults were included in this study from February 2011 to June 2012 at a health promotion center. Information of the lifestyles and presence of metabolic syndrome factors was obtained. Biochemical markers were measured and free oxygen radicals test (FORT) was performed on the blood. RESULTS: Of the 254 subjects, 86 (33.9%) had metabolic syndrome, and 187 (73.6%) were men. Between the subjects with and without metabolic syndrome, there was a significant increase in alanine aminotransferase and serum FORT values in the subjects with metabolic syndrome. Multiple linear regression analysis showed that high-sensitivity C-reactive protein (hs-CRP) (P = 0.004), metabolic syndrome (P = 0.037), and female gender (P = 0.030) were independent predictors of serum FORT values. The subjects with high fasting blood sugar level or low high density lipoprotein cholesterol levels showed high serum FORT values. CONCLUSION: High hs-CRP, the presence of metabolic syndrome, and female gender were associated with the high oxidative stress. High oxidative stress was associated with the presence of metabolic syndrome.

Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells.

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 µM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and ß corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3α and ß also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.