Lysophosphatidic acid responsive photosensitive supramolecular organic frameworks for tumor imaging, drug loading, and photodynamic therapy.

Supramolecular organic frameworks have been widely applied for biological detection and drug delivery. In this study, a supramolecular organic framework (SOF) is constructed through the self-assembly of a highly photosensitive triarylphosphine oxide guest molecule, OTPP-6-Methyl, with cucurbit [8] uril (CB [8]). The formation of the SOF gradually enhances the weak fluorescence of OTPP-6-Methyl owing to the restriction of the molecular folding motion. Although the high positive charge of OTPP-6-Methyl facilitates binding to various negatively charged substances, the SOF system only demonstrated an obvious fluorescence response to LPA, a biomarker of ovarian cancer, via the disassembly of SOF and subsequent binding of OTPP-6-Methyl with LPA. The fluorescence changes during the entire process are insufficient to allow the sensitive detection of LPA; thus, we further designed a FRET system by introducing Cy5, which can act as an energy receptor to achieve a ratiometric readout for LPA. The tumor-targeting cRGD group was introduced into the SOF system as part of another guest molecule, OTPP-5-M-1-cRGD, to improve the tumor-targeting ability of the SOF system. The SOF system further improves the photosensitivity of guest molecules, and is therefore used in the in vivo imaging of ovarian cancer subcutaneous tumors and as a DDS for loading DOX for the combined in vivo chemotherapy and photodynamic treatment of tumors.

Development and Validation of Potential Molecular Subtypes and Signatures of Thyroid Carcinoma Based on Aging-related Gene Analysis.

BACKGROUND/AIM: Thyroid carcinoma (THCA) is a cancer of the endocrine system that most commonly affects women. Aging-associated genes play a critical role in various cancers. Therefore, we aimed to gain insight into the molecular subtypes of thyroid cancer and whether senescence-related genes can predict the overall prognosis of THCA patients. MATERIALS AND METHODS: Thyroid carcinoma (THCA) transcriptome-related expression profiles were obtained from The Cancer Genome Atlas (TCGA) database. These profiles were randomly divided into training and validation subsets at a ratio of 1:1. Unsupervised clustering algorithms were used to compare differences between the two subtypes; prognosis-related senescence genes were used to further construct our prognostic models by univariate and multivariate Cox analyses and construct a nomogram to predict the 1-, 3-, and 5-year overall survival probability of THCA patients. In addition, we performed gene set enrichment analysis (GSEA) to predict the immune microenvironment and somatic mutations between the different risk groups. Finally, real-time PCR was used to verify the expression levels of key model genes. RESULTS: The 'ConsensusClusterPlus' R package was used to cluster thyroid cancer into two categories (Cluster1 and Cluster2) on the basis of 46 differentially expressed aging-related genes (DE-ARGs); patients in Cluster1 demonstrated a better prognosis than those in Cluster2. Cox analysis was used to screen six prognosis-related DE-ARGs. Finally, our real-time PCR results confirmed our hypothesis. CONCLUSION: Differences exist between the two subtypes of thyroid cancer that help guide treatment decisions. The six DE-ARG genes have a high predictive value for risk stratifying THCA patients.

The added value of AI-based computer-aided diagnosis in classification of cancer at prostate MRI.

OBJECTIVES: To develop an artificial intelligence (AI) model for prostate segmentation and prostate cancer (PCa) detection, and explore the added value of AI-based computer-aided diagnosis (CAD) compared to conventional PI-RADS assessment. METHODS: A retrospective study was performed on multi-centers and included patients who underwent prostate biopsies and multiparametric MRI. A convolutional-neural-network-based AI model was trained and validated; the reliability of different CAD methods (concurrent read and AI-first read) were tested in an internal/external cohort. The diagnostic performance, consistency and efficiency of radiologists and AI-based CAD were compared. RESULTS: The training/validation/internal test sets included 650 (400/100/150) cases from one center; the external test included 100 cases (25/25/50) from three centers. For diagnosis accuracy, AI-based CAD methods showed no significant differences and were equivalent to the radiologists in the internal test (127/150 vs. 130/150 vs. 125/150 for reader 1; 127/150 vs.132/150 vs. 131/150 for reader 2; all p > 0.05), whereas in the external test, concurrent-read methods were superior/equal to AI-first read (87/100 vs. 71/100, p < 0.001, for reader 2; 79/100 vs. 69/100, p = 0.076, for reader 1) and better than/equal to radiologists (79/100 vs. 72/100, p = 0.039, for reader 1; 87/100 vs. 86/100, p = 1.000, for reader 2). Moreover, AI-first read/concurrent read improved consistency in both internal test (κ = 1.000, 0.830) and external test (κ = 0.958, 0.713) compared to radiologists (κ = 0.747, 0.600); AI-first read method (8.54 s/7.66 s) was faster than readers (92.72 s/89.54 s) and concurrent-read method (29.15 s/28.92 s), respectively. CONCLUSION: AI-based CAD could improve the consistency and efficiency for accurate diagnosis; the concurrent-read method could enhance the diagnostic capabilities of an inexperienced radiologist in unfamiliar situations. KEY POINTS: • For prostate cancer segmentation, the performance of multi-small Vnet displays optimal compared to small Vnet and Vnet (DSCmsvnet vs. DSCsvnet, p = 0.021; DSCmsvnet vs. DSCvnet, p < 0.001). • For prostate gland segmentation, the mean/median DSCs for fine and coarse segmentation were 0.91/0.91 and 0.88/0.89, respectively. Fine segmentation displays superior performance compared to coarse (DSCcoarse vs. DSCfine, p < 0.001). • For PCa diagnosis, AI-based CAD methods improve consistency in internal (κ = 1.000; 0.830) and external (κ = 0.958; 0.713) tests compared to radiologists (κ = 0.747; 0.600); the AI-first read (8.54 s/7.66 s) was faster than the readers (92.72 s/89.54 s) and the concurrent-read method (29.15 s/28.92 s).

Solid Migration to Assemble a Flower-like Nanozyme with Highly Dense Single Copper Sites for Specific Phenol Oxidation.

Nanozymes with high catalytic stability and sustainability have emerged as powerful competitors to natural enzymes for diverse biocatalytic applications. However, constructing a nanozyme with high specificity is one of their biggest challenges. Herein, we develop a facile solid migration strategy to access a flower-like single copper site nanozyme (Cu SSN) via direct transformation of copper foam activated by 2-methylimidazole. With highly clustered CuN3 sites whose local structure is similar to that of natural polyphenol oxidase, the Cu SSN exhibits excellent activity and specificity to oxidize phenols without peroxidase-like activity. Furthermore, the Cu SSN shows high sensitivity in the colorimetric detection of epinephrine with a low detection limit of 0.10 µg mL-1, exceeding that of most previously reported enzyme-mimicking catalysts. This work not only provides a simple method for the large-scale preparation of high-performance nanozymes but also offers an inspiration for the design of highly specific nanozymes by mimicking the synergy among sites in natural enzymes.

Precise Regulation of Iron Spin States in Single FeN4 Sites for Efficient Peroxidase-Mimicking Catalysis.

The catalytic activity and selectivity of single-atom sites catalysts is strongly dependent on the supports structure and central metal coordination environment. However, the further optimization of electronic configuration to improve the catalytic performance is usually hampered by the strong coordination effect between the support and metal atoms. Herein, it is discovered that enzyme-mimicking catalytic performance can be enhanced at the fixed coordination single-atom Fe sites by regulating the Fe spin states. The X-ray absorption fine structure, 57 Fe Mössbauer spectrum, and temperature-dependent magnetization measurements reveal that the spin states of Fe in single FeN4  sites can be well manipulated via changing the pyrolysis temperature. The intermediate-spin Fe sites catalyst (t2g 4 eg 1) demonstrates a much higher peroxidase-mimicking activity in comparison with high-spin structure (t2g 3 eg 2). More importantly, the based enzymes system realizes sensitive detection of H2 O2  and glucose by colorimetric sensors with high catalytic activity and selectivity. Furthermore, theoretical calculations unveil that the intermediate-spin FeN4  promotes the OH* desorption process, thus greatly reducing the reaction energy barrier. These findings provide a route to design highly active enzyme-mimicking catalysts and an engineering approach for regulating spin states of metal sites to enhance their catalytic performance.

A Prospective, Self-Controlled Pilot Study of the Efficacy of Roxadustat for Erythropoietin Hyporesponsiveness in Patients Requiring Chronic Ambulatory Peritoneal Dialysis.

OBJECTIVES: The present study aimed to explore the efficacy and safety of roxadustat in patients with renal anemia and erythropoietin (EPO) hyporesponsive who are receiving continuous ambulatory peritoneal dialysis (CAPD). METHODS: This is a single center, before and after treatment, self-controlled study; 55 CAPD patients with renal anemia and EPO hyporesponsiveness were enrolled. The main follow-up parameters included routine blood, liver and kidney function, electrolyte, blood lipid, high-sensitivity C-reactive protein, and iron tests. Serum samples were used to determine interleukin-6 and tumor necrosis factor-α levels via enzyme linked immunosorbent assay. The Modified Quantitative Subjective Global Assessment Score and Malnutrition-Inflammation Score before and after treatment, and adverse events during treatment were recorded. The follow-up observation time was 12 weeks. Preliminary data 12-24 weeks before the enrollment as well as post-follow-up data at 36 weeks were also collected. RESULTS: Fifty patients completed the 12-week follow-up. The hemoglobin levels were 8.0 ± 1.2 g/dL at baseline and 11.2 ± 2.0 g/dL after 12 weeks of roxadustat treatment. The hemoglobin increases at all measured time points and was statistically significant compared with the baseline value (P < .05). The overall hemoglobin response rate (hemoglobin increase ≥ 1.0 g/dL) was 80%, and 50% of the patients reached the hemoglobin target (hemoglobin ≥ 11.0 g/dL) at 12 weeks. Transferrin was higher at 12 weeks (2.2 ± 0.5 g/L) than at baseline (1.7 ± 0.5 g/L) (P < .05), while serum ferritin levels slightly decreased compared with the baseline value (P > .05). The median high-sensitivity C-reactive protein level and other inflammation-related indicators, such as white blood cell counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, interleukin-6, and tumor necrosis factor-α, were not significantly different from their baseline values. Nutrition-related biochemical indices such as albumin, creatinine, and blood lipids were also not significantly changed. The Modified Quantitative Subjective Global Assessment Score and Malnutrition-Inflammation Score were slightly lower at 12 weeks than at baseline. No serious adverse events were observed during the follow-up period. Post-follow-up data revealed a maintained hemoglobin level in patients who remained on roxadustat treatment while those switched back to EPO treatment after 12 weeks resulted in a decreased hemoglobin at 36 weeks. CONCLUSIONS: In patients with EPO hyporesponsiveness on CAPD, roxadustat can efficiently and safely improve anemia and nutritional status without promoting inflammation.

Biocompatible Ruthenium Single-Atom Catalyst for Cascade Enzyme-Mimicking Therapy.

Rationally constructing single-atom enzymes (SAEs) with superior activity, robust stability, and good biocompatibility is crucial for tumor therapy but still remains a substantial challenge. In this work, we adopt biocompatible carbon dots as the carrier material to load Ru single atoms, achieving Ru SAEs with superior multiple enzyme-like activity and stability. Ru SAEs behave as oxidase, peroxidase, and glutathione oxidase mimics to synchronously catalyze the generation of reactive oxygen species (ROS) and the depletion of glutathione, thus amplifying the ROS damage and finally causing the death of cancer cells. Notably, Ru SAEs exhibit excellent peroxidase-like activity with a specific activity of 7.5 U/mg, which surpasses most of the reported SAEs and is 20 times higher than that of Ru/C. Theoretical results reveal that the electrons of the Ru 4d orbital in Ru SAEs are transferred to O atoms in H2O2 and then efficiently activate H2O2 to produce •OH. Our work may provide some inspiration for the design of SAEs for cancer therapy.

Compressive Strain Modulation of Single Iron Sites on Helical Carbon Support Boosts Electrocatalytic Oxygen Reduction.

Designing and modulating the local structure of metal sites is the key to gain the unique selectivity and high activity of single metal site catalysts. Herein, we report strain engineering of curved single atomic iron-nitrogen sites to boost electrocatalytic activity. First, a helical carbon structure with abundant high-curvature surface is realized by carbonization of helical polypyrrole that is templated from self-assembled chiral surfactants. The high-curvature surface introduces compressive strain on the supported Fe-N4 sites. Consequently, the curved Fe-N4 sites with 1.5 % compressed Fe-N bonds exhibit downshifted d-band center than the planar sites. Such a change can weaken the bonding strength between the oxygenated intermediates and metal sites, resulting a much smaller energy barrier for oxygen reduction. Catalytic tests further demonstrate that a kinetic current density of 7.922 mA cm-2 at 0.9 V vs. RHE is obtained in alkaline media for curved Fe-N4 sites, which is 31 times higher than that for planar ones. Our findings shed light on modulating the local three-dimensional structure of single metal sites and boosting the catalytic activity via strain engineering.

Cation-Exchange Induced Precise Regulation of Single Copper Site Triggers Room-Temperature Oxidation of Benzene.

The controllable synthesis of stable single-metal site catalysts with an expected coordination environment for high catalytic activity and selectivity is still challenging. Here, we propose a cation-exchange strategy for precise production of an edge-rich sulfur (S) and nitrogen (N) dual-decorated single-metal (M) site catalysts (M = Cu, Pt, Pd, etc.) library. Our strategy relies on the anionic frameworks of sulfides and N-rich polymer shell to generate abundant S and N defects during high-temperature annealing, further facilitating the stabilization of exchanged metal species with atomic dispersion and excellent accessibility. This process was traced by in situ transmission electron microscopy, during which no metal aggregates were observed. Both experiments and theoretical results reveal the precisely obtained S, N dual-decorated Cu sites exhibit a high activity and low reaction energy barrier in catalytic hydroxylation of benzene at room temperature. These findings provide a route to controllably produce stable single-metal site catalysts and an engineering approach for regulating the central metal to improve catalytic performance.

Comparison on radiation effective dose and image quality of right coronary artery on prospective ECG-gated method between 320 row CT and 2nd generation (128-slice) dual source CT.

This retrospective study was to compare the image quality of right coronary artery (RCA) and effective radiation dose on prospective ECG-gated method between 320 row computed tomography (CT) and 2nd generation (128-slice) dual source CT. A total of 215 candidates underwent CT coronary angiography using prospective ECG-gated method, 120 patients enrolled in 320 row CT group, and 95 patients in dual source CT group. We divided RCA image quality scores as 1/2/3/4, which means excellent/good/adequate/not assessable and heart rates were considered, as well as the radiation dose. There is no statistically significant difference of RCA image quality of Score 1/2 between 320 row CT and 2nd generation dual source CT, but lower heart rate (<70/min) improved RCA image quality. Meanwhile, the 2nd generation dual source CT scan have significant lower radiation dose. For patients with high level heart rate variation, both prospective ECG-gated method of 320 row CT scan (Toshiba) and 2nd generation dual source CT scan (Siemens) basically provided good image quality on RCA. There is an advantage of effective radiation dose reduction in prospective ECG-gated method using the 2nd generation dual source CT scan. After the iodine contrast agent was injected into elbow vein, the threshold triggering method was used to carry out prospective gated scanning, and the acquired fault image was reconstructed by the standard post-processing software of each manufacturer. The radiation dose value is obtained through the dose report automatically generated after each scan.

Single Iron Site Nanozyme for Ultrasensitive Glucose Detection.

Nanomaterials with enzyme-mimicking characteristics have engaged great awareness in various fields owing to their comparative low cost, high stability, and large-scale preparation. However, the wide application of nanozymes is seriously restricted by the relatively low catalytic activity and poor specificity, primarily because of the inhomogeneous catalytic sites and unclear catalytic mechanisms. Herein, a support-sacrificed strategy is demonstrated to prepare a single iron site nanozyme (Fe SSN) dispersed on the porous N-doped carbon. With well-defined coordination structure and high density of active sites, the Fe SSN performs prominent peroxidase-like activity by efficiently activating H2 O2 into hydroxyl radical (•OH) species. Furthermore, the Fe SSN is applied in colorimetric detection of glucose through a multienzyme biocatalytic cascade platform. Moreover, a low-cost integrated agarose-based hydrogel colorimetric biosensor is designed and successfully achieves the visualization evaluation and quantitative detection of glucose. This work expands the application of single-site catalysts in the fields of nanozyme-based biosensors and personal biomedical diagnosis.

A Supported Nickel Catalyst Stabilized by a Surface Digging Effect for Efficient Methane Oxidation.

A surface digging effect of supported Ni NPs on an amorphous N-doped carbon is described, during which the surface-loaded Ni NPs would etch and sink into the underneath carbon support to prevent sintering. This process is driven by the strong coordination interaction between the surface Ni atoms and N-rich defects. In the aim of activation of C-H bonds for methane oxidation, those sinking Ni NPs could be further transformed into thermodynamically stable and active metal-defect sites within the as-generated surface holes by simply elevating the temperature. In situ transmission electron microscopy images reveal the sunk Ni NPs dig themselves adaptive surface holes, which would largely prevent the migration of Ni NPs without weakening their accessibility. The reported two-step strategy opens up a new route to manufacture sintering-resistant supported metal catalysts without degrading their catalytic efficiency.

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

INTRODUCTION: Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. PARTICIPANTS AND DESIGN: In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level. SETTINGS: The study was performed in a clinical research center. RESULTS: Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 µg/ml, p<0.001), and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001). Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. CONCLUSION: Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

Combined effects of sex hormone-binding globulin and sex hormones on risk of incident type 2 diabetes.

BACKGROUND: The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). METHODS: A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008-13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. RESULTS: After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62-51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21-4.53], 0.14 [95% CI 0.10-0.74]; Ptrend = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. CONCLUSION: Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men.

Serum bisphenol A as a predictor of chronic kidney disease progression in primary hypertension: a 6-year prospective study.

OBJECTIVE: Hypertensive nephropathy is one of the major causes of chronic kidney disease (CKD). Bisphenol A (BPA) is associated with elevated blood pressure and urinary albuminuria. The aim of this study is to evaluate the association between serum BPA with the progression of CKD in patients with primary hypertension. METHODS: In this prospective study, 302 patients with primary hypertension were followed up for 6 years (195 men and 107 women, 65.29 ±â€Š9.78 years at baseline). The baseline values of serum BPA were measured. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation (eGFRcr-cys). Regression models were used to calculate associations of serum BPA with the annual change in eGFR and the risk of CKD progression. RESULTS: Baseline serum BPA concentration was 0.61(0.26, 2.44) ng/ml and was significantly negatively correlated with the annual change in eGFR (R = -0.197, P < 0.001). After adjusting for clinical factors, baseline serum BPA level had a significant negative association with the annual change in eGFR (ß = -0.132, P = 0.007). Univariate logistic regression analysis showed that the baseline age, SBP, eGFR, and serum BPA levels were predictors of CKD stage 3 or greater. In multivariate logistic regression analysis, patients with high serum BPA levels exhibited a five-fold increased risk of developing CKD stage 3 or greater compared with patients with low serum BPA levels [odds ratio 4.79 (95% confidence interval 1.81, 14.25), P = 0.004]. CONCLUSION: Serum BPA may be a predictor of CKD progression in patients with primary hypertension.

Serum bisphenol A and progression of type 2 diabetic nephropathy: a 6-year prospective study.

AIMS: Bisphenol A (BPA) is associated with diabetes and cardiovascular diseases. The aim of our study was to evaluate whether serum BPA could predict the progression of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). METHODS: In this prospective study, a total of 121 patients with T2D and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m(2) were followed up for 6 years. The baseline values of serum BPA were measured. Renal function was measured as eGFR calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation. Development of CKD was defined as eGFR < 60 mL/min/1.73 m(2) at the last follow-up. Regression models were used to analyze the associations of serum BPA with the change in eGFR and the risk of CKD development. RESULTS: Baseline serum BPA concentration was 0.40 (0.17, 1.40) ng/mL. Duration of T2D, baseline waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, and serum BPA level were significantly negatively associated with the annual change and percentage change in eGFR. After adjusting for clinical factors, baseline serum BPA level had a significant negative association with the annual change in eGFR (ß = -0.371, P < 0.001) and percentage change in eGFR (ß = -0.391, P = <0.001). Multivariate logistic regression analysis showed that patients with high levels of serum BPA exhibited about a sevenfold increased risk of developing CKD compared to patients with low levels of serum BPA [odds ratio (OR) 6.65 (95 % CI 1.47, 30.04), P = 0.014]. CONCLUSION: Serum BPA may be a predictor of CKD in patients with T2D.

AMP-kinase pathway is involved in tumor necrosis factor alpha-induced lipid accumulation in human hepatoma cells.

AIM: It is well known that lipid accumulation and inflammation are two important steps in pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD). However, fewer studies have explored the direct relationship between lipid accumulation and inflammation in early NAFLD. Tumor necrosis factor alpha (TNF-α) is one of the classical inflammatory cytokines. AMP-activated protein kinase (AMPK) is known as a critical regulator of energy homeostasis in metabolic processes. This study aims to investigate the role of TNF-α on lipid deposition of HepG2 cells and examine the modification of AMPK pathway. MAIN METHODS: TNF-α was added in HepG2 cells and lipid accumulation was analyzed by Oil Red O staining and quantitative test of triglyceride (TG). The expressions of phosphorylated AMPK and its pathway (including mTOR and SREBP-1) were determined. Furthermore, an AMPK agonist (metformin or AICAR) or antagonist (compound C) was co-administrated with TNF-α in HepG2 cells to investigate its effect on TNF-α induced lipid deposition. KEY FINDINGS: A significant increment of TG content in HepG2 cells was observed after TNF-α treatment. Meanwhile, substantially suppressed AMPK and ACC phosphorylation, enhanced mTOR and p70S6K phosphorylation, and increased protein expression of FAS and SREBP-1 were found. Co-treatment with metformin or AICAR decreased the TNF-α-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions. On the contrary, while co-incubated with compound C, AMPK and ACC phosphorylation were suppressed and the inhibitory effect of metformin on HepG2 cell lipid deposition was also attenuated. SIGNIFICANCE: Our results suggest that TNF-α directly induces lipid accumulation in HepG2 cells, at least in part, through the inhibition of AMPK/mTOR/SREBP-1 pathway.

Multichannel series piezoelectric quartz crystal cell sensor for real time and quantitative monitoring of the living cell and assessment of cytotoxicity.

A new multichannel series piezoelectric quartz crystal (MSPQC) cell sensor for real time monitoring of living cells in vitro was reported in this paper. The constructed sensor was used successfully to monitor adhesion, spreading, proliferation, and apoptosis of MG63 osteosarcoma cells and investigate the effects of different concentrations of cobalt chloride on MG63 cells. Quantitative real time and dynamic cell analyses data were conducted using the MSPQC cell sensor. Compared with methods such as fluorescence staining and morphology observation by microscopy, the MSPQC cell sensor is noninvasive, label free, simple, cheap, and capable of online monitoring. It can automatically record the growth status of cells and quantitatively evaluate cell proliferation and the apoptotic response to drugs. It will be a valuable detection and analysis tool for the acquisition of cellular level information and is anticipated to have application in the field of cell biology research or cytotoxicity testing in the future.

Rosiglitazone inhibits expression and secretion of PEDF in adipose tissue and liver of male SD rats via a PPAR-γ independent mechanism.

Pigment epithelium-derived factor (PEDF) plays an important role in insulin resistance (IR). The study aims to investigate the effect of rosiglitazone, an insulin sensitizer, on PEDF production and release both in vivo and in vitro. Male SD rats were divided into normal control group, high-fat group, and rosiglitazone group. Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 adipocytes and HepG2 cells were established by the hyperinsulinemic method. Glucose uptake was examined to validate IR of adipocytes, and phosphorylation of protein kinase B and glycogen synthesis kinase 3ß were examined to validate IR of HepG2 cells. Rosiglitazone, 2-chloro-5-nitro-N-phenylbenzamide (GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ), and compound C (inhibitor of AMP-activated protein kinase [AMPK]) were used for the in vitro intervention. In vivo, the high-fat group showed increased serum PEDF levels, which negatively correlated with insulin sensitivity, whereas the rosiglitazone treatment decreased the serum PEDF and down-regulated PEDF expression in fat and liver of the obese rats, concomitant with significantly enhanced insulin sensitivity. In vitro, the IR cells showed increased PEDF secretion and expression, whereas rosiglitazone lowered PEDF secretion and expression, accompanied with increased insulin sensitivity. Interestingly, combination with 2-chloro-5-nitro-N-phenylbenzamide did not influence the effect of rosiglitazone on PEDF. However, rosiglitazone stimulated AMPK phosphorylation in fat and liver of the obese rats, whereas in vitro, when combined with compound C, the effect of rosiglitazone on PEDF was abrogated. In summary, rosiglitazone inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation rather than peroxisome proliferator-activated receptor-γ, and changes of PEDF induced by rosiglitazone are closely associated with IR improvement.

Pessary reduction and postoperative cure of retention in women with anterior vaginal wall prolapse.

This study aimed to determine whether preoperative pessary reduction of anterior vaginal wall prolapse in patients with elevated postvoid residual (PVR) volumes relieves urinary retention, and if reconstructive pelvic surgery in these patients cures urinary retention. The records of all women with symptomatic anterior vaginal wall and urinary retention (PVR >or=100 cc) who underwent evaluation and surgical repair of the anterior vaginal wall at our institution between 1996 and 1999 were retrospectively reviewed. All patients underwent a detailed urogynecologic and urodynamic evaluation and had a pessary trial prior to surgery. Cure of urinary retention was defined as PVR <100 cc at 3 months postoperatively. Sensitivity, specificity, positive and negative predictive values for pessary reduction testing were calculated. Twenty-four patients met the inclusion criteria. Two patients (8%) had stage 2, eleven (46%) stage 3, and eleven (46%) stage 4 anterior vaginal wall prolapse. Preoperatively, the use of pessary was associated with relief of urinary retention in 75% patients. In predicting postoperative cure of urinary retention, pessary testing had a sensitivity of 89%, specificity of 80%, positive predictive value of 94%, and negative predictive value of 67%. Nineteen of 24 patients had a PVR <100 cc postoperatively, indicating a 79% cure rate for urinary retention. In women with symptomatic anterior vaginal wall prolapse and urinary retention, use of a pessary is associated with relief of retention in the majority of patients. Furthermore, pessary reduction testing has good sensitivity, specificity, and positive predictive value for postoperative voiding function.