Endothelial cell migration is essential for tumor angiogenesis, and interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis. This study aimed to investigate the molecular mechanism of IL-8 induced endothelial cell migration. Our results indicated that IL-8 induced a rapid rearrangement of the actin cytoskeleton in EA.Hy926 cells, generating extensions resembling membrane ruffling and stress fibers. These processes required parallel upregulation of the small GTPases Rac1 and RhoA. Moreover, we demonstrated that IL-8 activated PI3K following the same kinetics observed from IL-8 induction of cytoskeletal rearrangement, suggesting the participation of PI3K in these processes. Taken together, our study demonstrates that PI3K-Rac1/RhoA signaling pathway plays a vital role in IL-8 induced endothelial cell migration, and provides new insight into the molecular mechanisms by which IL-8 contributes to tumor angiogenesis and metastasis.

Abstract:Regional haze episodes have occurred frequently in eastern China over the past decades. As a critical indicator to evaluate air quality, the mass concentration of ambient fine particulate matters smaller than 2.5 µm in aerodynamic diameter (PM 2.5 ) is involved in many studies. To overcome the limitations of ground measurements on PM 2.5 concentration, which is featured in disperse representation and coarse coverage, many statistical models were developed to depict the relationship between ground-level PM 2.5 and satellite-derived aerosol optical depth (AOD). However, the current satellite-derived AOD products and statistical models on PM 2.5 -AOD are insufficient to investigate PM 2.5 characteristics at the urban scale, in that spatial resolution is crucial to identify the relationship between PM 2.5 and anthropogenic activities. This paper presents a geographically and temporally weighted regression (GTWR) model to generate ground-level PM 2.5 concentrations from satellite-derived 500 m AOD. The GTWR model incorporates the SARA (simplified high resolution MODIS aerosol retrieval algorithm) AOD product with meteorological variables, including planetary boundary layer height (PBLH), relative humidity (RH), wind speed (WS), and temperature (TEMP) extracted from WRF (weather research and forecasting) assimilation to depict the spatio-temporal dynamics in the PM 2.5 -AOD relationship. The estimated ground-level PM 2.5 concentration has 500 m resolution at the MODIS satellite's overpass moments twice a day, which can be used for air quality monitoring and haze tracking at the urban and regional scale. To test the performance of the GTWR model, a case study was carried out in a region covering the adjacent parts of Jiangsu, Shandong, Henan, and Anhui provinces in central China. A cross validation was done to evaluate the performance of the GTWR model. Compared with OLS, GWR, and TWR models, the GTWR model obtained the highest value of coefficient of determination (R 2 ) and the lowest values of mean absolute difference (MAD), root mean square error (RMSE), and mean absolute percentage error (MAPE).

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Background Mortality and other clinical outcomes between culture-negative and culture-positive septic patients have been documented inconsistently and are very controversial. A systematic review and meta-analysis was performed to compare the clinical outcomes of culture-negative and culture-positive sepsis or septic shock. Methods We searched the PubMed, Cochrane and Embase databases for studies from inception to the 1st of January 2021. We included studies involving patients with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality and clearly compared culture-negative versus culture-positive patients with clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, mechanical ventilation requirements, mechanical ventilation duration and renal replacement requirements). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). Results Seven studies including 22,655 patients were included. The primary outcome of this meta-analysis showed that there was no statistically significant difference in the all-cause mortality between two groups (OR = 0.95; 95% CI, 0.88 to 1.01; P = 0.12; Chi-2 = 30.71; I2 = 80%). Secondary outcomes demonstrated that there was no statistically significant difference in the ICU length of stay (MD = − 0.19;95% CI, − 0.42 to 0.04; P = 0.10;Chi-2 = 5.73; I2 = 48%), mechanical ventilation requirements (OR = 1.02; 95% CI, 0.94 to 1.11; P = 0.61; Chi2 = 6.32; I2 = 53%) and renal replacement requirements (OR = 0.82; 95% CI, 0.67 to 1.01; P = 0.06; Chi-2 = 1.21; I2 = 0%) between two groups. The hospital length of stay of culture-positive group was longer than that of the culture-negative group (MD = − 3.48;95% CI, − 4.34 to − 2.63; P < 0.00001;Chi-2 = 1.03; I2 = 0%). The mechanical ventilation duration of culture-positive group was longer than that of the culture-negative group (MD = − 0.64;95% CI, − 0.88 to − 0.4; P < 0.00001;Chi-2 = 4.86; I2 = 38%). Conclusions Culture positivity or negativity was not associated with mortality of sepsis or septic shock patients. Furthermore, culture-positive septic patients had similar ICU length of stay, mechanical ventilation requirements and renal replacement requirements as those culture-negative patients. The hospital length of stay and mechanical ventilation duration of culture-positive septic patients were both longer than that of the culture-negative patients. Further large-scale studies are still required to confirm these results.

Our results demonstrate for the first time that OGT-mediated O-GlcNAcylation promotes NF-κB signaling activation and inflammation in pancreatic acinar cells, which might promote the progression of AP.

D-Mannitol, one of the main phytochemicals of the edible Tamogi-take mushroom (Pleurotus cornucopiae), was found to inhibit an angiotensin I converting enzyme (ACE). The antihypertensive effect of D-mannitol and a hot water extract of Tamogi-take mushroom was demonstrated in spontaneously hypertensive rats (SHR) by oral administration.

Background: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Methods: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. Results: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57–0.63), 0.95 (95%CI = 0.93–0.96), 0.36 (95%CI = 0.28–0.48), 11.64 (95%CI = 5.85–23.14), and 38.94 (95%CI = 18.33–82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55–3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89–4.86; P < .01). Conclusion: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.

Background Isoflurane, a widely used anesthetic in surgery, has been found to induce neurotoxicity. In parallel, genistein is thought to attenuate isoflurane-induced neurotoxicity, although underlying molecular mechanisms are still unclear. In this study, we studied the protective effects of genistein on isoflurane-induced neuroinflammation in rats and BV2 cells. Methods Sprague-Dawley rat pups were exposed to 0.75% isoflurane for 6 hours at postnatal day 7 (P7), and genistein (20, 40, or 80 mg/kg/day) or saline administered from P3 to P15. Hippocampal single-cell suspensions were prepared and apoptosis analyzed by flow cytometry. mRNA expression was determined by RT-qPCR, while protein expression was assessed using Western blot, immunochemistry and immunofluorescence. TLR4 was knocked-out in BV2 cells through CRISPR-Cas9. Results Genistein treatment reduced isoflurane-induced apoptosis and inflammation in rat hippocampus. Importantly, genistein promoted M2 and suppressed M1 microglia polarization in rat hippocampus after stimulation with isoflurane. In addition, genistein reduced isoflurane-induced protein expression levels of TLR4, MyD88, TRAF6, p-TAK1, p-p38, p-ERK, p-IκBα and p-NF-κB in rat hippocampus. In BV2 cells exposed to isoflurane, genistein treatment decreased IL-1β, TNF-α, IL-6 and IL-8 mRNA expressions, promoted M2 and suppressed M1 microglia polarization. Similarly, genistein also decreased TLR4 protein levels in isoflurane-induced BV2 cells. However, genistein did not affect CD16, iNOS, CD206 and Arg1 protein levels in TLR4-KO BV2 cells exposed to isoflurane. Conclusion Genistein attenuates isoflurane-induced neurotoxicity by inhibiting TLR4-mediated microglial inflammation in vivo and in vitro.