The role of continuous glucose monitoring in physical activity and nutrition management: perspectives on present and possible uses.

PURPOSE: Continuous glucose monitoring (CGM) is on the rise as the prevalence of obesity and diabetes increases. This review aimed to explore the use of CGM and its potential novel applications in physical activity and nutrition management. METHODS: We searched PubMed, Web of Science, and Wiley Online Library databases using the keywords 'continuous glucose monitor,' 'nutrition,' 'physical activity,' and 'numerical modeling.' RESULTS: Continuous blood glucose measurement is useful for individuals with obesity and diabetes. Long-term blood glucose data allow for personalized planning of nutritional composition, meal timing, and physical activity type and intensity, as well as help prevent hypoglycemia and hyperglycemia. Thus, understanding the limitations of CGM is important for its effective use. CONCLUSION: CGM systems are being increasingly used to monitor and identify appropriate blood glucose controlling interventions. Blood glucose level is influenced by various factors such as nutrient composition, meal timing, physical activity, circadian rhythm, and cortisol levels. Numerical modeling can be used to analyze the complex relationship between stress, sleep, nutrition, and physical activity, which affect blood glucose levels. In future, blood glucose, sleep, and stress data will be integrated to predict appropriate lifestyle levels for blood glucose management. This integrated approach improves glucose control and overall wellbeing, potentially reducing societal costs.

Adipose Tissue-Derived Mesenchymal Stem Cells Extend the Lifespan and Enhance Liver Function in Hepatocyte Organoids.

In this study, we generated hepatocyte organoids (HOs) using frozen-thawed primary hepatocytes (PHs) within a three-dimensional (3D) Matrigel dome culture in a porcine model. Previously studied hepatocyte organoid analogs, spheroids, or hepatocyte aggregates created using PHs in 3D culture systems have limitations in their in vitro lifespans. By co-culturing adipose tissue-derived mesenchymal stem cells (A-MSCs) with HOs within a 3D Matrigel dome culture, we achieved a 3.5-fold increase in the in vitro lifespan and enhanced liver function compared to a conventional two-dimensional (2D) monolayer culture, i.e., more than twice that of the HO group cultured alone, reaching up to 126 d. Although PHs were used to generate HOs, we identified markers associated with cholangiocyte organoids such as cytokeratin 19 and epithelial cellular adhesion molecule (EPCAM). Co-culturing A-MSCs with HOs increased the secretion of albumin and urea and glucose consumption compared to HOs cultured alone. After more than 100 d, we observed the upregulation of tumor protein P53 (TP53)-P21 and downregulation of EPCAM, albumin (ALB), and cytochrome P450 family 3 subfamily A member 29 (CYP3A29). Therefore, HOs with function and longevity improved through co-culturing with A-MSCs can be used to create large-scale human hepatotoxicity testing models and precise livestock nutrition assessment tools.

SOX9 is a key component of RUNX2-regulated transcriptional circuitry in osteosarcoma.

BACKGROUND: The absence of prominent, actionable genetic alternations in osteosarcomas (OS) implies that transcriptional and epigenetic mechanisms significantly contribute to the progression of this life-threatening form of cancer. Therefore, the identification of potential transcriptional events that promote the survival of OS cells could be key in devising targeted therapeutic approaches for OS. We have previously shown that RUNX2 is a transcription factor (TF) essential for OS cell survival. Unfortunately, the transcriptional network or circuitry regulated by RUNX2 in OS cells is still largely unknown. METHODS: The TFs that are in the RUNX2 transcriptional circuitry were identified by analyzing RNAseq and ChIPseq datasets of RUNX2. To evaluate the effect of SOX9 knockdown on the survival of osteosarcoma cells in vitro, we employed cleaved caspase-3 immunoblotting and propidium iodide staining techniques. The impact of SOX9 and JMJD1C depletion on OS tumor growth was examined in vivo using xenografts and immunohistochemistry. Downstream targets of SOX9 were identified and dissected using RNAseq, pathway analysis, and gene set enrichment analysis. Furthermore, the interactome of SOX9 was identified using BioID and validated by PLA. RESULT: Our findings demonstrate that SOX9 is a critical TF that is induced by RUNX2. Both in vitro and in vivo experiments revealed that SOX9 plays a pivotal role in the survival of OS. RNAseq analysis revealed that SOX9 activates the transcription of MYC, a downstream target of RUNX2. Mechanistically, our results suggest a transcriptional network involving SOX9, RUNX2, and MYC, with SOX9 binding to RUNX2. Moreover, we discovered that JMJD1C, a chromatin factor, is a novel binding partner of SOX9, and depletion of JMJD1C impairs OS tumor growth. CONCLUSION: The findings of this study represent a significant advancement in our understanding of the transcriptional network present in OS cells, providing valuable insights that may contribute to the development of targeted therapies for OS.

Effect of Serum and Oxygen on the In Vitro Culture of Hanwoo Korean Native Cattle-Derived Skeletal Myogenic Cells Used in Cellular Agriculture.

Skeletal muscle-derived myogenic cells (SKMCs) are novel protein sources capable of replacing animal meat. However, SKMCs have not been commercialized owing to poor productivity and the high cost of in vitro cell culture. Therefore, we cultured SKMCs in varying serum (5-20%) and oxygen concentrations (5-20%) to investigate the parameters that most impact cell productivity (serum, hypoxia, and culture medium) and examined cell proliferation ability and genes involved in myogenesis/proliferation/apoptosis/reactive oxygen species (ROS). In fetal bovine serum (FBS) groups, hypoxia induction doubled cell number, and the 20% FBS/normoxia group exhibited similar cell numbers as 5% FBS/5% hypoxia, confirming that 5% hypoxia reduced serum requirement by four-fold. The use of 20% FBS downregulated MTF5/MYOD1/MYOG/MYH1, whereas hypoxia induction with ≤10% FBS upregulated them. Although 20% FBS lowered TERT expression through rapid cell proliferation, NOX1, a major factor of ROS, was suppressed. DMEM/F12 demonstrated better differentiation potential than F10 by upregulating MYF3/MYOD1/MYOG/MYH1 and downregulating MSTN, particularly DMEM/F12 with 2% FBS/5% hypoxia. The myogenic fusion index was higher in DMEM/F12 without FBS than in DMEM/F12 with FBS (0.5-5%); however, the total nuclei number was reduced owing to apoptosis. Therefore, high serum levels are essential in influencing SKMC growth, followed by hypoxia as a synergistic component.

Autophagy Inhibition as a Potential Therapeutic Strategy for Breast Cancer with Mitochondrial Translation Defect Caused by CBFB-Deficiency.

ABBREVIATIONS: AMPK, AMP-activated protein kinase; BioID, biotinylation identification; CBFB, core-binding factor subunit beta; HCQ, hydroxychloroquine; HNRNPK, heterogeneous nuclear ribonucleoprotein K; PDX, patient-derived xenograft; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; TUFM, Tu translation elongation factor, mitochondrial; ETC, electron transport chain.

Dysregulation of Mitochondrial Translation Caused by CBFB Deficiency Cooperates with Mutant PIK3CA and Is a Vulnerability in Breast Cancer.

Understanding functional interactions between cancer mutations is an attractive strategy for discovering unappreciated cancer pathways and developing new combination therapies to improve personalized treatment. However, distinguishing driver gene pairs from passenger pairs remains challenging. Here, we designed an integrated omics approach to identify driver gene pairs by leveraging genetic interaction analyses of top mutated breast cancer genes and the proteomics interactome data of their encoded proteins. This approach identified that PIK3CA oncogenic gain-of-function (GOF) and CBFB loss-of-function (LOF) mutations cooperate to promote breast tumor progression in both mice and humans. The transcription factor CBFB localized to mitochondria and moonlighted in translating the mitochondrial genome. Mechanistically, CBFB enhanced the binding of mitochondrial mRNAs to TUFM, a mitochondrial translation elongation factor. Independent of mutant PI3K, mitochondrial translation defects caused by CBFB LOF led to multiple metabolic reprogramming events, including defective oxidative phosphorylation, the Warburg effect, and autophagy/mitophagy addiction. Furthermore, autophagy and PI3K inhibitors synergistically killed breast cancer cells and impaired the growth of breast tumors, including patient-derived xenografts carrying CBFB LOF and PIK3CA GOF mutations. Thus, our study offers mechanistic insights into the functional interaction between mutant PI3K and mitochondrial translation dysregulation in breast cancer progression and provides a strong preclinical rationale for combining autophagy and PI3K inhibitors in precision medicine for breast cancer. SIGNIFICANCE: CBFB-regulated mitochondrial translation is a regulatory step in breast cancer metabolism and synergizes with mutant PI3K in breast cancer progression.

Highly permselective uric acid detection using kidney cell membrane-functionalized enzymatic biosensors.

Abnormal blood uric acid (UA) levels can lead to its crystallization in the joints, consequently resulting in gout. Accurate detection of UA in the blood is imperative for the early diagnosis of gout. However, electrochemical UA biosensors are vulnerable to antioxidants in the blood, limiting accurate UA detection. To address this issue, we focused on the function of uric acid transporter 1 (URAT1), which is selectively permeable to UA. URAT1 is abundant in the kidney cell membrane (KCM). To apply URAT1 to a sensor, we developed a KCM-coated UA biosensor (called the KCM sensor) that could selectively detect UA through URAT1. The KCM coating in the fabricated KCM sensor was verified via scanning electron microscopy, atomic force microscopy, and confocal microscopy. The KCM sensor enabled the detection of UA in the range of 0-1000 µM, with a limit of detection of 8.5 µM, suggesting that it allows the diagnosis of the early stages of gout. On the other hand, the UA permeability of the KCM sensor was significantly reduced in the presence of a URAT1 inhibitor, implying that URAT1 is a key factor for UA detection. The selectivity of the KCM sensor was demonstrated by measuring the amount for UA in the presence of various antioxidants. Finally, the KCM sensor was capable of measuring UA in human serum and was reproducible with 0.5-1.6% deviation. The UA permeability and selectivity of the KCM sensor were maintained even after 3 weeks of storage.

Fatty acid oxidation is required for embryonic stem cell survival during metabolic stress.

Metabolic regulation is critical for the maintenance of pluripotency and the survival of embryonic stem cells (ESCs). The transcription factor Tfcp2l1 has emerged as a key factor for the naïve pluripotency of ESCs. Here, we report an unexpected role of Tfcp2l1 in metabolic regulation in ESCs-promoting the survival of ESCs through regulating fatty acid oxidation (FAO) under metabolic stress. Tfcp2l1 directly activates many metabolic genes in ESCs. Deletion of Tfcp2l1 leads to an FAO defect associated with upregulation of glucose uptake, the TCA cycle, and glutamine catabolism. Mechanistically, Tfcp2l1 activates FAO by inducing Cpt1a, a rate-limiting enzyme transporting free fatty acids into the mitochondria. ESCs with defective FAO are sensitive to cell death induced by glycolysis inhibition and glutamine deprivation. Moreover, the Tfcp2l1-Cpt1a-FAO axis promotes the survival of quiescent ESCs and diapause-like blastocysts induced by mTOR inhibition. Thus, our results reveal how ESCs orchestrate pluripotent and metabolic programs to ensure their survival in response to metabolic stress.

CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer.

The CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete. Here, we analyze genetic interactions between mutations of CBFB and other highly mutated genes in human breast cancer datasets and find that CBFB and TP53 mutations are mutually exclusive, suggesting a functional association between CBFB and p53. Integrated genomic studies reveal that TAp73 is a common transcriptional target of CBFB and p53. CBFB cooperates with p53 to maintain TAp73 expression, as either CBFB or p53 loss leads to TAp73 depletion. TAp73 re-expression abrogates the tumorigenic effect of CBFB deletion. Although TAp73 loss alone is insufficient for tumorigenesis, it enhances the tumorigenic effect of NOTCH3 overexpression, a downstream event of CBFB loss. Immunohistochemistry shows that p73 loss is coupled with higher proliferation in xenografts. Moreover, TAp73 loss-of-expression is a frequent event in human breast cancer tumors and cell lines. Together, our results significantly advance our understanding of the tumor suppressive functions of CBFB and reveal a mechanism underlying the communication between the two tumor suppressors CBFB and p53.

Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts.

BACKGROUND: The liver is one of the vital organs involved in detoxification and metabolism. The sex-based differences between the functionality of male and female liver have been previously reported, i.e., male's liver are good in alcohol clearance and lipid metabolism, while female's liver are better in cholesterol metabolism. To date, studies on novel drug toxicity have not considered the sex-specific dimorphic nature of the liver. However, the use of hepatocyte-like cells to treat liver diseases has increased recently. METHODS: Mouse embryos were isolated from a pregnant female C57BL/6J mouse where mouse embryonic fibroblasts (MEFs) were isolated from back skin tissue of each embryo. MEFs were transduced with human transcription factors hHnf1α, hHnf4α, and hFoxa3 using the lentiviral system. The transduced MEFs were further treated with hepatocyte-conditioned media followed by its analysis through RT-qPCR, immunofluorescence, functional assays, and finally whole-transcriptome RNA sequencing analysis. For in vivo investigation, the mouse hepatocyte-like cells (miHep) were transplanted into CCl4-induced acute liver mouse model. RESULTS: In this study, we evaluated the sex-specific effect of miHep induced from male- and female-specific mouse embryonic fibroblasts (MEFs). We observed miHeps with a polygonal cytoplasm and bipolar nucleus and found that male miHeps showed higher mHnf4a, albumin secretion, and polyploidization than female miHeps. Transcriptomes from miHeps were similar to those from the liver, especially for Hnf4a of male miHeps. Male Cyps were normalized to those from females, which revealed Cyp expression differences between liver and miHeps. In both liver and miHeps, Cyp 4a12a and Cyp 4b13a/2b9 predominated in males and females, respectively. After grafting of miHeps, AST/ALT decreased, regardless of mouse sex. CONCLUSION: In conclusion, activation of endogenic Hnf4a is important for generation of successful sex-specific miHeps; furthermore, the male-derived miHep exhibits comparatively enhanced hepatic features than those of female miHep.

Reagent-Free Colorimetric Cholesterol Test Strip Based on Self Color-Changing Property of Nanoceria.

Paper-based test strip consisting of cerium oxide nanoparticles (nanoceria) as hydrogen peroxide (H2O2)-dependent color-changing nanozymes and cholesterol oxidase (ChOx) has been developed for convenient colorimetric determination of cholesterol without the need for chromogenic substrate. The construction of the cholesterol strip begins with physical adsorption of nanoceria on the paper surface, followed by covalent immobilization of ChOx via silanization, chitosan-mediated activation, and glutaraldehyde treatment of the nanoceria-embedded paper matrices. In the presence of cholesterol, ChOx catalyzes its oxidation to produce H2O2, which forms peroxide complex on the nanoceria surface and induces visual color change of the nanoceria-embedded paper from white/light yellow into intense yellow/orange, which was conveniently quantified with an image acquired by a conventional smartphone with the ImageJ software. Using this strategy, target cholesterol was specifically determined down to 40 µM with a dynamic linear concentration range of 0.1-1.5 mM under neutral pH condition, which is suitable to measure the serum cholesterol, with excellent stability during 20 days and reusability by recovering its original color-changing activity for 4 consecutive cycles. Furthermore, the practical utility of this strategy was successfully demonstrated by reliably determining cholesterol in human blood serum samples. This study demonstrates the potential of self color-changing nanozymes for developing colorimetric paper strip sensor, which is particularly useful in instrumentation-free point-of-care environments.

A Randomized Controlled Trial of Thermo-Sensitive Sol-Gel Anti-Adhesion Agent after Gynecologic Surgery.

Postoperative abdominal adhesions can lead to several adverse consequences such as pelvic pain, bowel obstruction, and infertility. We aimed to explore the anti-adhesion efficacy and safety of a thermo-sensitive sol-gel agent in patients who receive abdominopelvic surgery for benign gynecologic disease. This study was a randomized, controlled, single-blind clinical trial of women undergoing benign gynecologic surgery between January 2017 and December 2017. The patients were randomly assigned to three groups with a 1:1:1 ratio: experimental group (received the thermo-sensitive sol-gel agent), control group (untreated), and comparator group (received 4% icodextrin). Patients were followed for 4 weeks postoperatively, and efficacy was evaluated by performing the visceral slide test to identify adhesion formation. In total, 183 patients were enrolled in the study, and 178 (97.3%) completed the trial. The incidence rate of abdominal adhesion formation was significantly lower in the experimental group than in the control group (7.9% vs. 21.1%, p = 0.040); however, it was similar between the experimental and comparator groups (7.9% vs. 13.8%. p = 0.299). At 4 weeks, no differences in adhesion-related symptoms were observed between the experimental and control groups. Adverse events were mostly mild and did not differ significantly among the three groups (p = 0.375). In conclusion, use of a thermo-sensitive sol-gel agent was safe and effective to prevent abdominal adhesions after benign gynecologic surgeries.

Para-aortic lymph node recurrence after curative radiotherapy for cervical cancer.

OBJECTIVE: The para-aortic lymph nodes are one of the most common sites in recurrent cervical cancer. However, treatment strategies for para-aortic lymph node recurrence have not yet been established.This study aimed to evaluate the prognostic factors and treatment outcomes in patients with para-aortic lymph node recurrence after curative radiotherapy for cervical cancer. METHODS: We retrospectively reviewed patients who developed para-aortic lymph node recurrence following curative radiation therapy for cervical cancer from January 2001 and December 2014 at the Samsung Medical Center. Prognostic factors for overall survival after recurrence were analyzed by univariate and multivariate analyses. RESULTS: A total of 67 patients were included in the analysis. After a median follow-up of 24.0 months (range 4-155), the 3-year overall survival rate was 42.7%. 32 patients had isolated para-aortic lymph node recurrence (group 1), 21 patients had para-aortic lymph node recurrence combined with other lymph node recurrence (group 2), and 14 patients developed para-aortic lymph node recurrence with distant organ metastasis (group 3). The 3-year overall survival rates in groups 1, 2, and 3 were 60.8%, 42.1%, and 7.7%, respectively (p<0.001). In multivariate analysis, histologic type of squamous cell carcinoma (p=0.028), non-symptomatic recurrence (p=0.024), isolated para-aortic lymph node recurrence (p=0.008), and disease-free interval (p=0.008) were significant factors for survival. Among the patients with isolated para-aortic lymph node recurrence, survival rates differed significantly according to disease-free interval; the 3-year overall survival in patients with disease-free interval ≥12 months and disease-free interval <12 months was 69.6% and 37.5%, respectively (p<0.001). CONCLUSIONS: In patients with para-aortic lymph node recurrence from cervical cancer, histologic type, presence of symptoms, extent of disease, and disease-free interval were the prognostic factors for survival. Patients with isolated para-aortic lymph node recurrence with disease-free interval ≥12 months had higher survival outcomes at 3 years.

G-protein coupled receptor 64 (GPR64) acts as a tumor suppressor in endometrial cancer.

BACKGROUND: Endometrial cancer is the most common gynecological cancer. G-protein coupled receptor 64 (GPR64) belongs to a family of adhesion GPCRs and plays an important role in male fertility. However, the function of GPR64 has not been studied in endometrial cancer. Our objective is to investigate the role of GPR64 in endometrial cancer. METHODS: We examined the levels of GPR64 in human endometrioid endometrial carcinoma by immunohistochemistry analysis. To determine a tumor suppressor role of GPR64 in endometrial cancer, we used a siRNA loss of function approach in human endometrial adenocarcinoma cell lines. RESULTS: GPR64 levels were remarkably lower in 10 of 21 (47.62%) of endometrial carcinoma samples compared to control. Depletion of GPR64 by siRNA transfection revealed an increase of colony formation ability, cell proliferation, cell migration, and invasion activity in Ishikawa and HEC1A cells. The expression of Connexin 43 (Cx43), a member of the large family of gap junction proteins, was reduced through activation of AMP-activated protein kinase (AMPK) in Ishikawa cells with GPR64-deficicy. CONCLUSIONS: These results suggest that GPR64 plays an important tumor suppressor role in endometrial cancer.

Visuo-Haptic-Based Multimodal Feedback Virtual Reality Solution to Improve Anxiety Symptoms: A Proof-of-Concept Study.

With proper guidance, virtual reality (VR) can provide psychiatric therapeutic strategies within a simulated environment. The visuo-haptic-based multimodal feedback VR solution has been developed to improve anxiety symptoms through immersive experience and feedback. A proof-of-concept study was performed to investigate this VR solution. Nine subjects recently diagnosed with panic disorder were recruited, and seven of them eventually completed the trial. Two VR sessions were provided to each subject. Depression, anxiety, and VR sickness were evaluated before and after each session. Although there was no significant effect of the VR sessions on psychiatric symptoms, we could observe a trend of improvement in depression, anxiety, and VR sickness. The VR solution was effective in relieving subjective anxiety, especially in panic disorder without comorbidity. VR sickness decreased over time. This study is a new proof-of-concept trial to evaluate the therapeutic effect of VR solutions on anxiety symptoms using visuo-haptic-based multimodal feedback simultaneously.

Comparison of survival outcomes between minimally invasive surgery and conventional open surgery for radical hysterectomy as primary treatment in patients with stage IB1-IIA2 cervical cancer.

OBJECTIVE: To compare survival outcomes of minimally invasive surgery (MIS) and conventional open surgery for radical hysterectomy (RH) among patients with early-stage cervical cancer (CC). METHODS: We retrospectively identified stage IB1-IIA2 CC patients who underwent either laparoscopic or open Type C RH between 2000 and 2018. Patients' clinicopathologic characteristics and survival outcomes were compared according to the surgical approach. For a more robust statistical analysis, we narrowed the study population down to the patients with stage IB1 who underwent pre-operative MRI. RESULTS: In total, 435 and 158 patients were assigned to open surgery and MIS groups, respectively. MIS group had significantly less parametrial invasion (6.3% vs. 15.4%; P = 0.004). Despite similar proportions of patients received adjuvant treatment, concurrent chemoradiation therapy was performed less frequently in MIS group. After a median follow up of 114.8 months, the groups showed similar overall survival; however, MIS group displayed poorer progression-free survival (PFS; 5-year rate, 78.5% vs. 89.7%; P < 0.001). Multivariate analyses identified MIS as an independent poor prognostic factor for PFS (adjusted HR, 2.883; 95% CI, 1.711-4.859; P < 0.001). Consistent results were observed among 349 patients with stage IB1: MIS was associated with higher recurrence rates (adjusted HR, 2.276; 95% CI, 1.039-4.986; P = 0.040). However, MIS did not influence PFS of stage IB1 patients with cervical mass size ≤2 cm on pre-operative MRI (adjusted HR, 1.146; 95% CI, 0.278-4.724; P = 0.850). CONCLUSIONS: Overall, MIS RH was associated with higher recurrence rates than open RH in patients with early-stage CC. However, MIS was not a poor prognostic factor among those with stage IB1 and cervical mass size ≤2 cm on pre-operative MRI.

Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis.

While wound healing is completed, the epithelium functions to normalize the interstitial context by eliminating fibroblasts excited during matrix reconstruction. If not, tissues undergo pathologic fibrosis. Pulmonary fibrosis is a fatal and hardly curable disorder. We here tried to identify epithelium-derived cytokines capable of ameliorating pulmonary fibrosis. Human lung fibroblasts were inactivated in epithelial cell-conditioned media. Cystatin C (CST3) and growth differentiation factor 15 (GDF15) were found to be enriched in the conditioned media and to inhibit the growth and activation of lung fibroblasts by inactivating the TGF-Smad pathway. In mouse and human lungs with interstitial fibrosis, CST3 and GDF15 expressions were markedly reduced, and the restoration of these cytokines alleviated the fibrotic changes in mouse lungs. These results suggest that CST3 and GDF15 are bona fide regulators to prevent excessive proliferation and activation of fibroblasts in injured lungs. These cytokines could be potential therapeutics for ameliorating interstitial lung fibrosis.

Intravenous Anesthetic, Propofol Affects Synaptic Responses in Cerebellar Purkinje Cells.

OBJECTIVE: Propofol is an intravenously administered anesthetic that enhances γ-aminobutyric acid-mediated inhibition in the central nerve system. Other mechanisms may also be involved in general anesthesia. Propofol has been implicated in movement disorders. The cerebellum is important for motor coordination and motor learning. The aim of the present study was to investigate the propofol effect on excitatory synaptic transmissions in cerebellar cortex. METHODS: Excitatory postsynaptic currents by parallel fiber stimulation and complex spikes by climbing fiber stimulation were monitored in Purkinje cells of Wister rat cerebellar slice using whole-cell patch-clamp techniques. RESULTS: Decay time, rise time and amplitude of excitatory postsynaptic currents at parallel fiber Purkinje cell synapses and area of complex spikes at climbing fiber Purkinje cell synapses were significantly increased by propofol administration. CONCLUSION: The detected changes of glutamatergic synaptic transmission in cerebellar Purkinje cell, which determine cerebellar motor output, could explain cerebellar mechanism of motor deficits induced by propofol.

CST3 and GDF15 ameliorate renal fibrosis by inhibiting fibroblast growth and activation.

The final strategies to care patients with end-stage renal fibrosis rely on dialysis and kidney transplantation. Because such treatments are invasive and cause health problems eventually, it is necessary to develop new therapeutic strategies for delaying the disease progress. We here searched for cytokines showing an anti-fibrotic activity in cell-based experiments. Cystatin C (CST3) and Growth differentiation factor 15 (GDF15) were identified to have anti-fibrotic activities in a cytokine array screening. In primary fibroblasts isolated from the mouse kidneys subjected to ureteral obstruction-induced fibrosis, each cytokine induced apoptotic cell death and reduced collagen production. These anti-fibrotic effects were further augmented by co-administration of both cytokines. Mechanistically, CST3 and GDF15 were found to block the TGF-ß receptor and the N-Myc signaling pathways, respectively. In mice with unilateral ureter obstruction, each cytokine and the combination of two cytokines effectively reduced the fibrotic burden in the subjected kidneys. Therefore, we propose that CST3 and GDF15 could be potential candidates for biopharmaceutics to ameliorate renal fibrosis.

The Impact of Organizational Commitment and Nursing Organizational Culture on Job Satisfaction in Korean American Registered Nurses.

PURPOSE: This study aimed to describe the perceived level of organizational commitment and organizational culture of Korean American Registered Nurses (KARNs) and to investigate predictors of job satisfaction. DESIGN: A total of 163 KARNs working in U.S. hospitals responded to a Web survey. Descriptive analysis, t test, analysis of variance, and stepwise regressions were used for data analysis. RESULTS: KARNs reported moderate levels of job satisfaction (3.5 ± 0.58). Job satisfaction was positively correlated with both organizational commitment ( r = .85, p < .001) and culture ( r = .66, p < .001). KARNs who were aged ≥50, married, hospital-employed, had longer nursing experience, and experienced turnover at least once were more likely to report higher job satisfaction compared with other nurses. Organizational commitment, culture, marital status, and workplace were significant predictors of and explained 76.8% of the variance in job satisfaction. CONCLUSION: This study provides evidence to help nursing managers and health policy makers develop educational programs aimed at enhancing job satisfaction and retention of KARNs.