In-situ mechanochemically tailorable 2D gallium oxyselenide for enhanced optoelectronic NO2 gas sensing at room temperature.

The adverse effects of NO2 on the environment and human health promote the development of high-performance gas sensors to address the need for monitoring. Two-dimensional (2D) metal chalcogenides have been considered an emerging group of NO2-sensitive materials, while incomplete recovery and low long-term stability are the two major hurdles for their practical implementation. The transformation into oxychalcogenides is an effective strategy to alleviate these drawbacks, but usually requires multiple-step synthesis and lacks controllability. Here, we prepare tailorable 2D p-type gallium oxyselenide with the thicknesses of 3-4 nm, through a single-step mechanochemical synthesis that combines the in-situ exfoliation and oxidation of bulk crystals. The optoelectronic NO2 sensing performances of such 2D gallium oxyselenide with different oxygen contents are investigated at room temperature, in which 2D GaSe0.58O0.42 exhibits the largest response magnitude of 82.2% towards 10 ppm NO2 at the irradiation of UV, with full reversibility, excellent selectivity, and long term stability for at least one month. Such overall performances are significantly improved over those of reported oxygen-incorporated metal chalcogenide-based NO2 sensors. This work provides a feasible approach to prepare 2D metal oxychalcogenides in a single-step manner and demonstrates their great potential for room-temperature fully reversible gas sensing.

PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.

The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic-specific deletion of PPDPF profoundly inhibits tumor development in KRASG12D -driven genetic mouse models of PDAC. PPDPF can bind GTP and transfer GTP to SOS1. Mutations of the GTP-binding sites severely impair the tumor-promoting effect of PPDPF. Consistently, mutations of the critical amino acids mediating SOS1-PPDPF interaction significantly impair the GEF activity of SOS1. Therefore, this study demonstrates a novel model of KRAS activation via PPDPF-SOS1 axis, and provides a promising therapeutic target for PDAC.

Posterolateral approach for posterior malleolus fixation in ankle fractures: functional and radiological outcome based on Bartonicek classification.

INTRODUCTION: Posterolateral approach has been advocated for the treatment of ankle fractures involving the posterior malleolus and satisfactory results were demonstrated in several studies. The Bartonicek classification based on 3-dimensional CT scanning was commonly used for treatment recommendation of posterior malleolar fracture (PMF). The aim of this retrospective study was to evaluate the clinical effect of the posterolateral approach for the treatment of PMF and present outcomes of patients with different types of Bartonicek classification. METHOD: We retrospectively reviewed the clinical outcomes of 72 patients with ankle fractures involving posterior malleolus (PM) from January 2016 to December 2018. Posterior malleolus fractures (PMFs) were all directly reduced and fixed by a posterolateral approach using lag screws and/or buttress plates. AOFAS score and VAS pain score were used as the primary functional outcome measures. The radiographic evaluation included the quality of the reduction and Kellgren-Lawrence (KL) osteoarthritis classification. According to the CT-based Bartonicek classification, all patients were classified into three groups: 42 type II, 18 type III and 12 type IV. Bartonicek type II patients were further divided into subtype IIa 19 cases, subtype IIb 16 cases and subtype IIc 7 cases. The radiological and functional outcomes were analyzed among different types and subtypes of Bartonicek classification. RESULTS: Sixty-eight patients (94.5%) achieved good or excellent reduction of PMF after surgery. The mean AOFAS score was 81.35 ± 6.15 at 6 months and 90.56 ± 4.98 at the final follow-up, respectively. The VAS score was 6.62 ± 1.03 one week after surgery, and 1.20 ± 0.92 at the final follow-up. Radiological evaluation at the final follow-up showed that primary bone union was achieved in all patients and 65 patients (88.9%) got no (KL grade 0) or just doubtable (KL grade 1) post-traumatic osteoarthritis. AOFAS scores decreased significantly with the severity of Bartonicek classification at 6 month (p < 0.001) and final follow-up (p < 0.05), while there was no statistical difference of VAS pain score among different types of Bartonicek classification. Reduction quality and the presence of osteoarthritis was not correlated to Bartonicek classification either. Besides, AOFAS scores at the final follow-up were statistically different among three subtypes of Bartonicek type II fractures (p < 0.05), and Bartonicek subtype IIa fractures had the highest AOFAS scores as 93 ± 4.99. Presence and severity of osteoarthritis was lower in patients with subtype IIa PMF compared to other subtype groups, this finding was statistically significant (p < 0.05). CONCLUSION: The posterolateral approach could achieve good clinical outcomes in the treatment of posterior malleolus fracture. Patients with a Bartonicek type II fracture had a better functional outcome measured by the AOFAS score compared to other types. Bartonicek type IIa fractures got a higher AOFAS score and a lower incidence of osteoarthritis at the final follow-up than the other two subtypes. Classification of PMFs according to the Bartonicek classification was reliable.

Atomically dispersed golds on degradable zero-valent copper nanocubes augment oxygen driven Fenton-like reaction for effective orthotopic tumor therapy.

Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl4 allows for the fabrication of different atomic ratios of AuxCuy. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au0.02Cu0.98 composition reveals the enhanced •OH generation following O2 → H2O2 → •OH. The degradable Au0.02Cu0.98 released Cu+ and Cu2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au0.02Cu0.98 for O2 → H2O2 → •OH as well. Instead of using endogenous H2O2, H2O2 can be sourced from the O2 in the air through the use of nanocubes. Notably, the Au0.02Cu0.98 structure is degradable and renal-clearable.

Passive smoking and urinary oxidative biomarkers: A pilot study of healthy travelers from Los Angeles to Beijing.

There is a great heterogeneity in smoking prevalence and tobacco control policy across different countries. However, it is unknown whether this heterogeneity could cause increased passive smoking and adverse health effects among international travelers. In this pilot study, we collected 190 urine samples from 26 Los Angeles residents before (LA-before), during (Beijing), and after (LA-after) a 10-week visit to Beijing to measure biomarkers of passive smoking (cotinine), exposure to polycyclic aromatic hydrocarbons (OH-PAHs), and oxidative stress (malondialdehyde, 8-isoprostane, and uric acid). The geometric mean concentrations of urinary cotinine were 0.14, 1.52, and 0.22 µg/g creatinine in LA-before, Beijing, and LA-after, respectively. Likewise, OH-PAH levels were significantly higher in Beijing as compared to LA-before or LA-after, in association with the urinary cotinine levels. One-fold increase in urinary cotinine levels was associated with 10.1% (95% CI: 5.53-14.8%), 8.75% (95% CI: 2.33-15.6%), and 25.4% (95%CI: 13.1-39.1%) increases in urinary levels of malondialdehyde, 8-isoprotane, and uric acid, respectively. OH-PAHs mediated 9.1-23.3% of the pro-oxidative effects associated with passive smoking. Taken together, our findings indicate that traveling to a city with higher smoking prevalence may increase passive smoking exposure, in association with pro-oxidative effects partially mediated by PAHs.

Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with systemic inflammation, yet what mechanisms regulate PAHs' inflammatory effects are less understood. This study evaluated the change of arachidonic acid (ARA) metabolites and inflammatory biomarkers in response to increased exposure to PAHs among 26 non-smoking healthy travelers from Los Angeles to Beijing. Traveling from Los Angeles to Beijing significantly increased urinary metabolites of dibenzofuran (800%), fluorene (568%), phenanthrene (277%), and pyrene (176%), accompanied with increased C-reactive protein, fibrinogen, IL-8, and IL-10, and decreased MCP-1, sCD40L, and sCD62P levels in the blood. Meanwhile, the travel increased the levels of ARA lipoxygenase metabolites that were positively associated with a panel of pro-inflammatory biomarkers. Concentrations of cytochrome P450 metabolite were also increased in Beijing and were negatively associated with sCD62P levels. In contrast, concentrations of ARA cyclooxygenase metabolites were decreased in Beijing and were negatively associated with anti-inflammatory IL-10 levels. Changes in both inflammatory biomarkers and ARA metabolites were reversed 4-7 weeks after participants returned to Los Angeles and were associated with urinary PAH metabolites, but not with other exposures such as secondhand smoke, stress, or diet. These results suggested possible roles of ARA metabolic alteration in PAHs-associated inflammatory effects.

BMP10 suppresses hepatocellular carcinoma progression via PTPRS-STAT3 axis.

Bone morphogenetic protein 10 (BMP10), one member of the BMP family, is involved in various development events. Dysregulation of BMP10 has been observed in several diseases, including hypertensive cardiac hypertrophy, Hirschsprung disease and blood vessel formation. However, its role in liver cancer remains largely unknown. In this study, we reported that BMP10 was significantly downregulated in HCC at both mRNA and protein level. Decreased BMP10 was associated with bigger tumor size, worse TNM stage, earlier recurrence and poorer survival. BMP10 negatively regulated HCC cell proliferation in vitro and in vivo. Mechanism study revealed that BMP10 suppressed tumor cell growth by inhibiting STAT3 signaling. Interestingly, we found that cytoplasmic BMP10 interacted with both receptor protein tyrosine phosphatase sigma (PTPRS) and STAT3, which facilitated dephosphorylation of STAT3 by PTPRS. Altogether, our study has revealed the clinical significance of BMP10 in HCC, and suppression of HCC cell growth by BMP10 via PTPRS-STAT3 axis, providing a potential therapeutic strategy for targeting STAT3 signaling in HCC.

Diesel Exhaust Induces Mitochondrial Dysfunction, Hyperlipidemia, and Liver Steatosis.

OBJECTIVE: Air pollution is associated with increased cardiovascular morbidity and mortality, as well as dyslipidemia and metabolic syndrome. Our goal was to dissect the mechanisms involved. Approach and Results: We assessed the effects of exposure to air pollution on lipid metabolism in mice through assessment of plasma lipids and lipoproteins, oxidized fatty acids 9-HODE (9-hydroxyoctadecadienoic) and 13-HODE (13-hydroxyoctadecadienoic), lipid, and carbohydrate metabolism. Findings were corroborated, and mechanisms were further assessed in HepG2 hepatocytes in culture. ApoE knockout mice exposed to inhaled diesel exhaust (DE, 6 h/d, 5 days/wk for 16 weeks) exhibited elevated plasma cholesterol and triglyceride levels, increased hepatic triglyceride content, and higher hepatic levels of 9-HODE and 13-HODE, as compared to control mice exposed to filtered air. A direct effect of DE exposure on hepatocytes was demonstrated by treatment of HepG2 cells with a methanol extract of DE particles followed by loading with oleic acid. As observed in vivo, this led to increased triglyceride content and significant downregulation of ACAD9 mRNA expression. Treatment of HepG2 cells with DE particles and oleic acid did not alter de novo lipogenesis but inhibited total, mitochondrial, and ATP-linked oxygen consumption rate, indicative of mitochondrial dysfunction. Treatment of isolated mitochondria, prepared from mouse liver, with DE particles and oleic acid also inhibited mitochondrial complex activity and ß-oxidation. CONCLUSIONS: DE exposure leads to dyslipidemia and liver steatosis in ApoE knockout mice, likely due to mitochondrial dysfunction and decreased lipid catabolism.

CHML promotes liver cancer metastasis by facilitating Rab14 recycle.

Metastasis-associated recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC), however, the underlying mechanisms remain largely elusive. In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, associated with poor survival, early recurrence and more satellite nodules in HCC patients. CHML promotes migration, invasion and metastasis of HCC cells, in a Rab14-dependent manner. Mechanism study reveals that CHML facilitates constant recycling of Rab14 by escorting Rab14 to the membrane. Furthermore, we identify several metastasis regulators as cargoes carried by Rab14-positive vesicles, including Mucin13 and CD44, which may contribute to metastasis-promoting effects of CHML. Altogether, our data establish CHML as a potential promoter of HCC metastasis, and the CHML-Rab14 axis may be a promising therapeutic target for HCC.

Liver cancer: WISP3 suppresses hepatocellular carcinoma progression by negative regulation of ß-catenin/TCF/LEF signalling.

OBJECTIVES: Wnt1-inducible signalling pathway protein 3 (WISP3/CCN6) belongs to the CCN (CYR61/CTGF/NOV) family of proteins, dysregulation of this family contributed to the tumorigenicity of various tumours. In this study, we need to explore its role in hepatocellular carcinoma that remains largely elusive. MATERIALS AND METHODS: The expression of WISP3/CCN6 was analysed by qRT-PCR and Western blotting. Effects of WISP3 on proliferation and metastasis of HCC cells were examined, respectively, by MTT assay and Boyden Chamber. Roles of WISP3 on HCC tumour growth and metastatic ability in vivo were detected in nude mice. Related mechanism study was confirmed by immunofluorescence and Western blotting. RESULTS: The expression of WISP3 was significantly downregulated in HCC clinical samples and cell lines, and reversely correlated with the tumour size. Forced expression of WISP3 in HCC cells significantly suppressed cell growth and migration in vitro as well as tumour growth and metastatic seeding in vivo. In contrast, downregulation of WISP3 accelerated cell proliferation and migration, and promoted in vivo metastasis. Further study revealed that WISP3 inhibited the translocation of ß-catenin to the nucleus by activating glycogen synthase kinase-3ß (GSK3ß). Moreover, constitutively active ß-catenin blocked the suppressive effects of WISP3 on HCC. CONCLUSIONS: Our study showed that WISP3 suppressed the progression of HCC by negative regulation of ß-catenin/TCF/LEF signalling, providing WISP3 as a potential therapeutic candidate for HCC.

Generation and characterization of a paclitaxel-resistant human gastric carcinoma cell line.

The main aim of this study was to establish a novel paclitaxel (PTX)-resistant human gastric carcinoma cell line and to investigate its biological significance. A cell line, MGC803/PTX, was established by gradually increasing PTX density on the basis of MGC803 over a period of 10 months. In addition, a pair of resistant cell lines (SW620 and SW620/PTX) were added to further explain the resistant mechanism of PTX. The drug resistance index and stability of MGC803/PTX cells were detected using the Cell Counting Kit-8 method. The morphological features were observed using inverted microscopy. Apoptosis was measured by flow cytometry (FCM) and Hoechst 33258 fluorescence staining. The distribution of the cell cycle was determined by FCM, and protein expressions of P-gp, Bcl-2, Bax, and PARP were detected by western blot analysis. When characterizing the resistance in vitro, we found that MGC803/PTX cells were 10.3-fold more resistant to PTX compared with MGC803 cells. In addition, MGC803/PTX cells showed cross-resistance to 5-fluorouracil and adriamycin. FCM and Hoechst 33258 fluorescence staining indicated that MGC803/PTX cells had a significantly lower percentage of apoptotic cells after treatment with PTX compared with MGC803 cells. Other differences between parental cells and resistant cells included morphology, proliferation rate, doubling time, cell cycle distribution, and colony-formation rate. Western blot analysis indicated that P-gp, Bcl-2, and PARP protein were more abundant in MGC803/PTX and SW620/PTX cells compared with MGC803 and SW620 cells, whereas Bax protein levels were lower in resistant cells. Furthermore, MGC803/PTX cells showed obvious resistance to PTX in vivo. To our knowledge, this is the first report on the establishment of a PTX-resistant MGC803 cell line, which is an important tool to explore the resistance of anticancer drugs and to overcome tumor drug resistance.

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

BACKGROUND: Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. METHODS AND RESULTS: Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. CONCLUSIONS: The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure.

Activation of the "Splenocardiac Axis" by electronic and tobacco cigarettes in otherwise healthy young adults.

The "Splenocardiac Axis" describes an inflammatory signaling network underlying acute cardiac ischemia, characterized by sympathetic nerve stimulation of hematopoietic tissues, such as the bone marrow and spleen, which then release proinflammatory monocytes that populate atherosclerotic plaques, thereby promoting ischemic heart disease. Electronic (e) cigarettes, like tobacco cigarettes trigger sympathetic nerve activation, but virtually nothing is known about their influence on hematopoietic and vascular tissues and cardiovascular risks. The objective of this study was to determine if the Splenocardiac Axis is activated in young adults who habitually use either tobacco or e-cigarettes. In otherwise healthy humans who habitually use tobacco cigarettes or e-cigarettes (not both), we used 18F-flurorodeoxyglucose positron emission tomography/computer tomography (FDG-PET/CT) to test the hypothesis that tobacco or e-cigarettes increased metabolic activity of the hematopoietic and vascular tissues. FDG uptake in the spleen increased from nonuser controls (1.62 ± 0.07), to the e-cigarette users (1.73 ± 0.04), and was highest in tobacco cigarette smokers (1.82 ± 0.09; monotone P = 0.05). Similarly, FDG uptake in the aorta increased from the nonuser controls (1.87 ± 0.07) to the e-cigarette users (1.98 ± 0.07), and was highest in tobacco cigarette smokers (2.10 ± 0.07; monotone P = 0.04). FDG uptake in the skeletal muscle, which served as a control tissue, was not different between the groups. In conclusion, these findings are consistent with activation of the Splenocardiac Axis by emissions from tobacco cigarettes and e-cigarettes. This activation suggests a mechanism by which tobacco cigarettes, and potentially e-cigarettes, may lead to increased risk of future cardiovascular events.

Gene expression profiling and pathway network analysis of anti-tumor activity by Jaridon 6 in esophageal cancer.

Jaridon 6, a novel ent-kaurene diterpenoid derived from Rabdosia rubescens (Hemsl.) Hara, possesses strong anti-tumor activity in esophageal cancer cells. In this study, we explored the underlying molecular events of the anti-tumor activity of Jaridon 6. Cell viability and apoptosis results obtained by flow cytometry confirmed the tumor inhibitory effect of Jaridon 6 in esophageal cancer cells. A cDNA microarray was performed and the observations were validated using quantitative reverse transcription polymerase chain reaction. The microarray data showed that 151 genes were differentially expressed between the untreated group and the Jaridon 6-treated group, among these were 57 upregulated genes, and 94 downregulated genes (P < 0.01, fold change threshold: 2). These included genes such as Wnt, peroxisome, and genes involved in chemokine signaling pathways. In addition, Western blot analysis demonstrated that Jaridon 6 regulated the expression of Wnt pathway proteins, including reduced levels of Dvl 2, survivin and cyclin D1, and increased levels of p-ß-catenin, and AXIN2 in EC109 and EC9706 esophageal cancer cells. In addition, recombinant murine Wnt3a could change the regulation of Jaridon 6 on Wnt pathway proteins. Immunohistochemical analysis indicated that the anti-tumor activity of Jaridon 6 was closely related to the Wnt signaling pathway in esophageal cancer cells.

Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users: Implications for Cardiovascular Risk.

Importance: Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. Objective: To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. Design, Setting, and Participants: Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non-tobacco cigarette, non-e-cigarette user control participants. Main Outcomes and Measures: Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. Results: Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B-containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. Conclusions and Relevance: In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.

EphB3 Stimulates Cell Migration and Metastasis in a Kinase-dependent Manner through Vav2-Rho GTPase Axis in Papillary Thyroid Cancer.

Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attentions. In the present study, we explored the function of EphB3, one member of Eph family, in papillary thyroid cancer (PTC). We found that the expression of EphB3 was significantly elevated in PTC. Either overexpression of EphB3 or activation of EphB3 by EfnB1-Fc/EfnB2-Fc stimulated in vitro migration of PTC cells. In contrast, siRNA-mediated knockdown of EphB3 or EphB3-Fc treatment, which only blocked EphB3-mediated forward signaling, inhibited migration and metastasis of PTC cells. A mechanism study revealed that EphB3 knockdown led to suppressed activity of Rac1 and enhanced activity of RhoA. Moreover, we found that Vav2, an important regulator of Rho family GTPases, was activated by EphB3 in a kinase-dependent manner. Altogether, our work suggested that EphB3 acted as a tumor promoter in PTC by increasing the in vitro migration as well as the in vivo metastasis of PTC cells through regulating the activities of Vav2 and Rho GTPases in a kinase-dependent manner.

Decreased Toll-like receptor-2 messenger ribonucleic acid and increased Toll-like receptor-4 in the tubal epithelium next to the infiltrated trophoblasts during tubal pregnancy.

OBJECTIVE: To explore the expression patterns of Toll-like receptor (TLR)2 and TLR4 in the tubal epithelial cells next to the infiltrated trophoblasts at the maternal-fetal interface during tubal pregnancy. DESIGN: Prospective, observational study. SETTING: University-based obstetrics and gynecology hospital. PATIENT(S): Thirty-seven women undergoing salpingectomy for tubal ampullary pregnancy and nine nonpregnant patients with benign uterine or appendix disease. INTERVENTION(S): Oviduct tissues with ectopic gestations were separated into implantation site (group 1) and nonimplantation site (group 2). Tissues from ampullary fallopian tubes during mid-secretory phase (group 3) were collected as the control group. Immunohistochemistry and quantitative real-time polymerase chain reaction were performed. MAIN OUTCOME MEASURE(S): Differences of TLR2 and TLR4 expression patterns between group 1 and group 2 and between the pregnant group (combined group 1 and group 2) and the nonpregnant group (group 3). RESULT(S): Comparing the pregnant group with group 3, TLR4 messenger RNA (mRNA) and protein were both significantly up-regulated in the pregnant group. In contrast, TLR2 mRNA was significantly down-regulated, whereas TLR2 protein showed a tendency toward reduction. Detailed analysis between group 1 and group 3 revealed statistically significantly higher TLR2 and TLR4 protein in group 1. In terms of mRNA, TLR4 expression was still shown to be significantly increased in group 1, whereas TLR2 expression was markedly decreased in group 1. CONCLUSION(S): Decreased TLR2 mRNA and increased TLR4 in the tubal epithelial cells next to the infiltrated trophoblasts may be associated with aspects of the pathophysiology of tubal ectopic pregnancy in immune defense.

Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway.

Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone injury and/or in scaffolds for bone replacement strategies. Finally, isolation of SDA-Col I from deer antler represents a renewable, green, and uncomplicated way to obtain a biomedically valuable therapeutic.

Synthesis and properties of novel water-soluble fullerene-glycine derivatives as new materials for cancer therapy.

Novel water-soluble fullerene-glycine derivatives were synthesized by means of simple organic chemistry. They are completely soluble in water, yielding a clear brown solution. The products were characterized by fourier transform infrared (FTIR), ultraviolet-visible spectroscopy (UV-Vis), (1)H NMR, (13)C NMR, thermogravimetric analyses (TGA), and scanning electron microscopy (SEM). The assembly behavior of water-soluble fullerene-glycine derivatives was investigated by SEM. The results show that the fullerene-glycine derivatives create morphology that is sphere-like. The cytotoxicity to cancer cell lines of the fullerene-glycine derivatives was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and flow cytometry. The results show that fullerene-glycine derivatives exhibit mortality and apoptosis of the cells which increased with the increase of fullerene-glycine derivative concentration. The cytotoxicity mechanism of fullerene-glycine derivatives was investigated for the first time. Novel water-soluble fullerene-glycine derivatives were synthesized by means of simple organic chemistry. The products were characterized by FTIR, UV-Vis, (1)H NMR, (13)C NMR, TGA, and SEM. The bioactivities of fullerene-glycine derivative materials have been tested, and the results show that compared with the fullerene complex, the fullerene-glycine derivative materials exhibit mortality and apoptosis of the cells which increased with the increase of fullerene-glycine derivative concentration. SEM images showed the macrostructure of fullerene-glycine derivative materials was spheres.

Cigarette smoking is associated with dose-dependent adverse effects on paraoxonase activity and fibrinogen in young women.

CONTEXT: Smoking is associated with increased fibrinogen and decreased paraoxonase (PON) activity, markers of inflammation and oxidative stress, in patients with coronary artery disease. OBJECTIVE: We tested the hypothesis that the adverse effect of smoking on these biomarkers of inflammation and oxidative stress would be detectable in otherwise healthy young female habitual smokers. MATERIALS AND METHODS: Thirty-eight young women participated in the study (n = 20 habitual smokers, n = 18 non-smokers). Fibrinogen, PON-1 activity and HDL oxidant index (HOI) were measured. RESULTS: Mean values of fibrinogen, PON-1 activity and log HOI were not different between the groups. Importantly, however, decreased PON-1 activity (rs = -0.51, p = 0.03) and increased fibrinogen (rs = 0.49, p = 0.04) were significantly correlated with increasing number of cigarettes smoked per day in habitual smokers. DISCUSSION AND CONCLUSION: Cigarette smoking is associated with a dose-dependent adverse effect on PON-1 activity and fibrinogen in young women, which may have implications for future cardiovascular risk.