Experimental design in this study.

<p>Experimental design in this study.</p

LPS increased but SB202190 and baicalin reduced nitrites production.

<p>^*<i>P</i><0.05, ^**<i>P</i><0.01 vs. control group; ^#<i>P</i><0.05, ^##<i>P</i><0.01 vs. LPS; ^§<i>P</i><0.05; ^§§<i>P</i><0.01 vs. LPS plus baicalin group.</p

LPS increased but baicalin reduced LPS-mediated TLR4 and PPARγ overexpression and phosphorylation.

<p>A: Representative gels for TLR4, PPARγ and p-PPARγ expression. B: Semiquantitation of TLR4, PPARγ and p-PPARγ in each group. ^*<i>P</i><0.05, ^**<i>P</i><0.01 vs. saline group; ^#<i>P</i><0.05, ^##<i>P</i><0.01 vs. LPS group.</p

siRNA duplexes used in this study

<p>siRNA duplexes used in this study</p

SR-202 antagonised the inhibitory effect of baicalin on p38 phosphorylation.

<p>A: Representative gels for p-p38 expression. B: Semiquantitation of p-p38 in each group. ^*<i>P</i><0.05, ^**<i>P</i><0.01 vs. LPS group; ^#<i>P</i><0.05, ^##<i>P</i><0.01 vs. LPS plus baicalin group.</p

SR-202 antagonised the inhibitory effect of baicalin on iNOS mRNA expression.

<p>A: Representative gels for iNOS mRNA expression. B: Semiquantitation of iNOS in each group. ^*<i>P</i><0.05, ^**<i>P</i><0.01 vs. LPS group. ^#<i>P</i><0.05, ^##<i>P</i><0.01 vs. LPS plus baicalin group.</p

LPS induced but siRNAs and baicalin inhibited p38 and ATF2 phosphorylation.

<p>A, C: Representative gels for p-38 and p-ATF2 expression. β-actin and lamin B are the internal controls. B, D: Semiquantitation of p-p38 and p-ATF2 in each group. ^*<i>P</i><0.05, ^**<i>P</i><0.01 vs. saline group; ^#<i>P</i><0.05, ^##<i>P</i><0.01 vs. LPS group.</p

Hyaluronic Acid Molecular Weight Determines Lung Clearance and Biodistribution after Instillation

Hyaluronic acid (HA) has emerged as a versatile polymer for drug delivery. Multiple commercial products utilize HA, it can be obtained in a variety of molecular weights, and it offers chemical handles for cross-linkers, drugs, or imaging agents. Previous studies have investigated multiple administration routes, but the absorption, biodistribution, and pharmacokinetics of HA after delivery to the lung is relatively unknown. Here, pharmacokinetic parameters were investigated by delivering different molecular weights of HA (between 7 and 741 kDa) to the lungs of mice. HA was labeled with either a near-infrared dye or with iodine-125 conjugated to HA using a tyrosine linker. In initial studies, dye-labeled HA was instilled into the lungs and fluorescent images of organs were collected at 1, 8, and 24 h post administration. Data suggested longer lung persistence of higher molecular weight HA, but signal diminished for all molecular weights at 8 h. To better quantitate pharmacokinetic parameters, different molecular weights of iodine-125 labeled HA were instilled and organ radioactivity was determined after 1, 2, 4, 6, and 8 h. The data showed that, after instillation, the lungs contained the highest levels of HA, as expected, followed by the gastrointestinal tract. Smaller molecular weights of HA showed more rapid systemic distribution, while 67 and 215 kDa HA showed longer persistence in the lungs. Lung exposure appeared to be optimum in this size range due to the rapid absorption of <67 kDa HA and the poor lung penetration and mucociliary clearance of viscous solutions of HA > 215 kDa. The versatility of HA molecular weight and conjugation chemistries may, therefore, provide new opportunities to extend pulmonary drug exposure and potentially facilitate access to lymph nodes draining the pulmonary bed

Phospholipid Composition Modulates Carbon Nanodiamond-Induced Alterations in Phospholipid Domain Formation

The focus of this work is to elucidate how phospholipid composition can modulate lipid nanoparticle interactions in phospholipid monolayer systems. We report on alterations in lipid domain formation induced by anionically engineered carbon nanodiamonds (ECNs) as a function of lipid headgroup charge and alkyl chain saturation. Using surface pressure vs area isotherms, monolayer compressibility, and fluorescence microscopy, we found that anionic ECNs induced domain shape alterations in zwitterionic phosphatidylcholine lipids, irrespective of the lipid alkyl chain saturation, even when the surface pressure vs area isotherms did not show any significant changes. Bean-shaped structures characteristic of dipalmitoylphosphatidylcholine (DPPC) were converted to multilobed, fractal, or spiral domains as a result of exposure to ECNs, indicating that ECNs lower the line tension between domains in the case of zwitterionic lipids. For membrane systems containing anionic phospholipids, ECN-induced changes in domain packing were related to the electrostatic interactions between the anionic ECNs and the anionic lipid headgroups, even when zwitterionic lipids are present in excess. By comparing the measured size distributions with our recently developed theory derived by minimizing the free energy associated with the domain energy and mixing entropy, we found that the change in line tension induced by anionic ECNs is dominated by the charge in the condensed lipid domains. Atomic force microscopy images of the transferred anionic films confirm that the location of the anionic ECNs in the lipid monolayers is also modulated by the charge on the condensed lipid domains. Because biological membranes such as lung surfactants contain both saturated and unsaturated phospholipids with different lipid headgroup charges, our results suggest that when studying potential adverse effects of nanoparticles on biological systems the role of lipid compositions cannot be neglected

DataSheet_1_A population-based predictive model identifying optimal candidates for primary and metastasis resection in patients with colorectal cancer with liver metastatic.zip

BackgroundThe survival benefit of primary and metastatic resection for patients with colorectal cancer with liver metastasis (CRLM) has been observed, but methods for discriminating which individuals would benefit from surgery have been poorly defined. Herein, a predictive model was developed to stratify patients into sub-population based on their response to surgery.MethodsWe assessed the survival benefits for adults diagnosed with colorectal liver metastasis by comparing patients with curative surgery vs. those without surgery. CRLM patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were identified for model construction. Other data including CRLM patients from our center were obtained for external validation. Calibration plots, the area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram compared with the tumor–node–metastasis (TNM) classification. The Kaplan–Meier analysis was performed to examine whether this model would distinguish patients who could benefit from surgery.ResultsA total of 1,220 eligible patients were identified, and 881 (72.2%) underwent colorectal and liver resection. Cancer-specific survival (CSS) for the surgery group was significantly better than that for the no-surgery group (41 vs. 14 months, p ConclusionsAn accurate and easy-to-use CRLM nomogram has been developed and can be applied to identify optimal candidates for the resection of primary and metastatic lesions among CRLM patients.</p