Parthenolide attenuates LPS-induced activation of NF-κB in a time-dependent manner in rat myocardium.

Parthenolide (PTN), a selective nuclear factor kappa B (NF-κB) inhibitor, has been used extensively to inhibit NF-κB activation. The duration of the inhibitory effect of PTN on NF-κB in vivo remains unclear. This study was to determine whether a lipopolysaccharide (LPS) challenge 6, 12 and 24 h after the administration of PTN could activate NF-κB. Rats were devided into five groups. The rats in the PTN, PTN+LPS and DMSO groups were injected intraperitoneally with PTN or DMSO. After 6, 12 or 24 h, LPS was administered in LPS and PTN+LPS groups. The expressions of NF-κB p50, IκBα and p-IκBα were inhibited in both PTN and PTN+LPS group at end of 6 and 12 h and no effects at 24 h. In summary, myocardial NF-κB expression occurs 1 h after the administration of LPS. PTN blocks this effect given at 6 h and no inhibitory effect 24 h after administration in vivo

Expression of CD44v6 and Its Association with Prognosis in Epithelial Ovarian Carcinomas

The aim of this study was to evaluate CD44v6 protein expression and its prognostic value of CD44v6 in ovarian carcinoma. The expression of CD44v6 was analyzed in 62 patients with ovarian carcinoma by immunohistochemical method. The data obtained were analyzed by univariate and multivariate analyses. The present study clearly demonstrates that tumor tissues from 41 (66.1%) patients showed positive expression with CD44v6. The expression of CD44v6 was significantly correlated with histological type, FIGO stage and histological grade of ovarian carcinomas. Concerning the prognosis, the survival period of patients with CD44v6 positive was shorter than that of patients with CD44v6 negative (36.6% versus 66.7%, 5-year survival, P < 0.05). Univariate analysis showed that CD44v6 expression, histological type, FIGO stage and histological grade were associated with 5-year survival, and CD44v6 expression was associated with histological type, FIGO stage and histological grade and 5-year survival. In multivariate analysis, using the COX-regression model, CD44v6 expression was important prognostic factor. In conclusion, these results suggest that CD44v6 may be related to histological type, FIGO stage and histological grade of ovarian carcinomas, and CD44v6 may be an important molecular marker for poor prognosis in ovarian carcinomas

Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro.

Transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signaling pathways play important roles in the proliferation and differentiation of lens epithelial cells (LECs) during development. Low dosage bFGF promotes cell proliferation while high dosage induces differentiation. TGFβ signaling regulates LEC proliferation and differentiation as well, but also promotes epithelial-mesenchymal transitions that lead to cataracts. Thus far, it has been difficult to recapitulate the features of germinative LECs in vitro. Here, we have established a LEC culture protocol that uses SB431542 (SB) compound to inhibit TGFβ/Smad activation, and found that SB treatment promoted mouse LEC proliferation, maintained LECs' morphology and distinct markers including N-cadherin, c-Maf, Prox1, and αA-, αB-, and β-crystallins. In contrast, low-dosage bFGF was unable to sustain those markers and, combined with SB, altered LECs' morphology and β-crystallin expression. We further found that Matrigel substrate coatings greatly increased cell proliferation and uniquely affected β-crystallin expression. Cultured LECs retained the ability to differentiate into γ-crystallin-positive lentoids by high-dosage bFGF treatment. Thus, a suppression of TGFβ/Smad signaling in vitro is critical to maintaining characteristic features of mouse LECs, especially expression of the key transcription factors c-Maf and Prox1

Diethyl 6,13-dioxo-5,7,12,13b,13c,14-hexa­hydro-6H,13H-5a,6a,12a,13a-tetra­azabenz[5,6]azuleno[2,1,8-ija]benz[f]azulene-13b,13c-dicarboxyl­ate 1,2-dichloro­ethane solvate

In the title inclusion compound, C26H26N4O6·C2H4Cl2, the solvent mol­ecule occupies a cavity inside the clip-type mol­ecule which is based on the glycoluril skeleton with two ethyl acetate substituents on the convex face of the glycoluril system. The dihedral angle between the aromatic rings of the host is 43.59 (4)° and the centroid–centroid distance is 6.741 (5) Å. The 1,2-dichloro­etane mol­ecule adopts a gauche conformation enabling it to participate in C—H⋯π inter­actions with the host. The packing motif in the title compound differs from that observed in the crystal structures of the host and in the benzene solvate. The host mol­ecules are linked into tapes by π–π stacking inter­actions (centroid–centroid distance = 3.733 Å) and are further assembled into layers via C—H⋯O inter­actions. One of the ethyl groups is disorded over two positions with site-occupancy factors of 0.702 (14) and 0.298 (14)

Dexmedetomidine post-treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF-1α signalling.

Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in the apoptotic process during cardiac ischaemia/reperfusion (I/R) injury. This study aimed to investigate whether post-treatment with dexmedetomidine (DEX) could protect against I/R-induced cardiac apoptosis in vivo and in vitro via regulating HIF-1α signalling pathway. Rat myocardial I/R was induced by occluding the left anterior descending artery for 30 minutes followed by 6-hours reperfusion, and cardiomyocyte hypoxia/reoxygenation (H/R) was induced by oxygen-glucose deprivation for 6 hours followed by 3-hours reoxygenation. Dexmedetomidine administration at the beginning of reperfusion or reoxygenation attenuated I/R-induced myocardial injury or H/R-induced cell death, alleviated mitochondrial dysfunction, reduced the number of apoptotic cardiomyocytes, inhibited the activation of HIF-1α and modulated the expressions of apoptosis-related proteins including BCL-2, BAX, BNIP3, cleaved caspase-3 and cleaved PARP. Conversely, the HIF-1α prolyl hydroxylase-2 inhibitor IOX2 partly blocked DEX-mediated cardioprotection both in vivo and in vitro. Mechanistically, DEX down-regulated HIF-1α expression at the post-transcriptional level and inhibited the transcriptional activation of the target gene BNIP3. Post-treatment with DEX protects against cardiac I/R injury in vivo and H/R injury in vitro. These effects are, at least in part, mediated via the inhibition of cell apoptosis by targeting HIF-1α signalling

Cold Dark Matter Isocurvature Perturbations: Cosmological Constraints and Applications

In this paper we present the constraints on cold dark matter (CDM) isocurvature contributions to the cosmological perturbations. By employing Markov Chain Monte Carlo method (MCMC), we perform a global analysis for cosmological parameters using the latest astronomical data, such as 7-year Wilkinson Microwave Anisotropy Probe (WMAP7) observations, matter power spectrum from the Sloan Digital Sky Survey (SDSS) luminous red galaxies (LRG), and "Union2" type Ia Supernovae (SNIa) sample. We find that the correlated mixture of adiabatic and isocurvature modes are mildly better fitting to the current data than the pure adiabatic ones, with the minimal $\chi^2$ given by the likelihood analysis being reduced by 3.5. We also obtain a tight limit on the fraction of the CDM isocurvature contributions, which should be less than 14.6% at 95% confidence level. With the presence of the isocurvature modes, the adiabatic spectral index becomes slightly bigger, n_s^{\rm adi}=0.972\pm0.014~(1\,\sigma), and the tilt for isocurvature spectrum could be large, namely, the best fit value is n_s^{\rm iso}=3.020. Finally, we discuss the effect on WMAP normalization priors, shift parameter R, acoustic scale l_A and z_{*}, from the CDM isocurvaure perturbation. By fitting the mixed initial condition to the combined data, we find the mean values of R, l_A and z_{*} can be changed about 2.9\sigma, 2.8\sigma and 1.5\sigma respectively, comparing with those obtained in the pure adiabatic condition.Comment: 9 pages, 5 figures, 3 tables, references adde

Transversus abdominis plane block reduces remifentanil and propofol consumption, evaluated by closed-loop titration guided by bispectral index.

The present prospective, randomized, double-blind study aimed to determine the impact of transversus abdominis plane (TAP) block on propofol and remifentanil consumption, when administered by closed-loop titration guided by processed electroencephalography, i.e., bispectral index (BIS) values. Following institutional review board approval, 60 patients were scheduled for laparoscopic colectomy under general anesthesia. Patients were randomly assigned to receive bilateral TAP block with 20 ml 0.375% ropivacaine (TAP group) or 20 ml 0.9% saline [control (CON) group]. General anesthesia was maintained with propofol and remifentanil administration using closed-loop titration guided by BIS values. The primary outcome was perioperative propofol and remifentanil consumption. The secondary outcomes were hypertensive or hypotensive events requiring treatment, recovery time in PACU and time to first rescue analgesia following surgery. A total of 58 patients participated in the present study. At similar depths of anesthesia, as measured by BIS during the maintenance phase (45-55), patients who received TAP blocks required less propofol (4.2±1.3 vs. 5.5±1.6 mg/kg/h; P&lt;0.001) and remifentanil (0.16±0.05 vs. 0.21±0.05 µg/kg/min; P&lt;0.001). Time to extubation was significantly shorter in the TAP group (9.8±3.2 min) than in the CON group (14.2±4.9 min) (P&lt;0.05). The requirement to treat hemodynamic change was also significantly lower (P&lt;0.05). Pain score at 2 h after surgery was also significantly reduced in the TAP group compared with the CON group (P&lt;0.05), whereas the time to first rescue analgesia was delayed in patients who received TAP block (P&lt;0.05). Postoperative nausea and vomiting occurred at comparable rates in each group (P&gt;0.05). In conclusion, TAP block combined with general anesthesia reduced propofol and remifentanil consumption, shortened time to tracheal extubation and promoted hemodynamic stability in laparoscopic colectomy