Search

This work presents an analytical method for determining vertical dynamic impedance and displacement response factor of a rigid cylindrical foundation embedded in unsaturated poroelastic soils. The foundation is assumed to be perfectly boned to its surrounding soil and its overlying half-space of unsaturated poroelastic soil, subjected to harmonic vertical loadings. The soil surrounding the circumference of the cylinder is modeled as a number of infinitely thin horizontal soil layers. Based on the Biot-type soil constitutive model, the equations governing the interaction of unsaturated soils with the cylindrical foundation are derived. Solutions are obtained by solving ordinary differential equations transformed from partial differential governing equations using the Hankel transform. The proposed solutions are verified against existing solutions of benchmark elastodynamic problems for embedded cylindrical foundations in dry and saturated soils. Using the derived solutions, several influencing parameters defining the stiffness and mass of the foundation system are examined to investigate the dynamics of the foundation interacting with it adjacent soils. It is concluded that the dynamic displacement response factor is sensitive to soil saturation. It is believed that the proposed solution should be beneficial to dynamic design with cylindrical foundations embedded in unsaturated soils. [ABSTRACT FROM AUTHOR]

Ischemia–reperfusion (I/R) injury is a common pathophysiological condition in ischemic stroke, involving various pathophysiological events, such as inflammation, cytotoxicity, neuronal loss and disruption of the blood–brain barrier (BBB). Rosavin is the major bioactive ingredient of Rhodiola Rosea L. with multiple therapeutic effects. The purpose of this was to investigate the role of rosavin in I/R‐induced cerebral injury. A cell oxygen–glucose deprivation and reoxygenation (OGD/R) model and a mouse middle cerebral artery occlusion (MCAO) model were established to induce I/R injury in vitro and in vivo, respectively. MCAO‐treated mice and OGD/R‐challenged human brain microvascular endothelial cells (HBMVECs) were administrated with or without rosavin at various concentrations. Rosavin‐treated mice showed reduced infarct volume, neuronal loss and neuronal cytotoxicity in I/R‐injured brains. Rosavin treatment downregulated the expression of pro‐inflammatory cytokines, reduced apoptosis and inhibited the activation of nuclear factor κ B in I/R‐injured mice and HBMVECs. Administration with rosavin also alleviated mouse brain oedema and upregulated tight junction proteins in mouse brains after I/R injury, suggesting that rosavin protected mice against I/R‐induced BBB disruption. Further analysis revealed that rosavin reduced the BBB permeability in I/R‐injured mice and HBMVECs by inhibiting autophagy. Moreover, rosavin intervention inhibited I/R injury‐induced activation of the mitogen‐activated protein kinase (MAPK) pathway and upregulation of matrix metalloproteinases in both mouse and cell models. In conclusion, rosavin protects the BBB against I/R injury possibly by regulating the MAPK pathway. The above results provide a rationale for further exploration of rosavin as a therapeutic candidate for cerebral I/R injury. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a life‐threatening form of a respiratory disorder, and there are few effective therapies. Abscisic acid (ABA) has been proven to be effective in influenza and asthma. Herein, we explored the protective effect of ABA on the resolution of ARDS and the underlying mechanism. Mice were challenged with lipopolysaccharide (LPS) to establish an ARDS model. We found that ABA reduced pulmonary injury, with concomitant suppression of endoplasmic reticulum (ER) stress and reduction of reactive oxygen species (ROS) production. Furthermore, after the elimination of ROS by the specific inhibitor N‐acetyl‐L‐cysteine (NAC), ABA did not further inhibit airway inflammation or ER stress in ARDS mice. In addition, ABA inhibited ROS production through nuclear factor erythroid 2–related factor 2 (Nrf2) activation in parallel with elevated levels of peroxisome proliferator activated receptor γ (PPAR‐γ). Furthermore, the addition of a PPAR‐γ antagonist abrogated the suppressive action of ABA on inflammation as well as on ER stress and oxidative stress, while NAC restored the protective effect of ABA in ARDS mice treated with a PPAR‐γ antagonist. Collectively, ABA protects against LPS‐induced lung injury through PPAR‐γ signaling, and this effect may be associated with its inhibitory effect on ROS‐mediated ER stress. [ABSTRACT FROM AUTHOR]

Unresolved inflammation underpins the pathogenesis of allergic airway diseases, such as asthma. Ketamine, accepted as a promising therapy for resistant asthma, has been demonstrated to attenuate allergic airway inflammation. However, the anti-inflammatory mechanism by ketamine in this setting is largely unknown. We aimed to investigate whether autophagy was involved in the protective effect of ketamine on allergic airway inflammation. Female C57BL/6 mice were sensitized to ovalbumin (OVA) and treated with ketamine at 25, 50, or 100 mg/kg prior to OVA challenge. In this model, the pulmonary morphological findings and airway inflammation were significantly inhibited at 50 mg/kg but not at 25 or 100 mg/kg. Moreover, 50 mg/kg ketamine abrogated the increased concentrations of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of allergic mice, as well as activated the expression of phosphorylated mammalian target of rapamycin (p-MTOR) and inhibited autophagy in allergic mice. To confirm whether the effect of 50 mg/kg ketamine on asthma was mediated by inhibiting autophagy, rapamycin was administered to mice sensitized to OVA and exposed to 50 mg/kg ketamine. All of the effect of 50 mg/kg ketamine was reversed by rapamycin treatment, including increased p-MTOR and decreased autophagy. Taken together, the present study demonstrates that 50 mg/kg ketamine inhibits allergic airway inflammation by suppressed autophagy, and this effect is mediated by the activation of MTOR in the lungs of allergic mice. [ABSTRACT FROM AUTHOR]

Background: Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process.Methods: Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue.Results: We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1β in BALF.Conclusion: Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model. [ABSTRACT FROM AUTHOR]

Molybdenum oxide nanomaterials have received increasing attention in recent years for their strong localized surface plasmon resonance (LSPR) absorption in the near-infrared (NIR) region and pH-dependent degradability. However, the rapid degradation of MoOx at physiological pH values would decrease the NIR photothermal effect. Here, we designed and prepared PEGMa–MoOx/p(NIPAM-co-MAA) microgels (NCs) exhibiting adjustable degradation. For that purpose, PEGMa (Mn = 400) modified MoOx was synthesized through a simple hydrothermal process. Then, PEGMa–MoOx with existing C=C groups was continually polymerized with NIPAM and MAA through emulsion polymerization. MAA was introduced to provide an acidic microenvironment (pH at 3–5) to control the degradation rate of PEGMa–MoOx. The photothermal efficiency of the NCs could be maintained at 54% even after 14 days. Meanwhile, the NCs also displayed a pH-dependent thermal response. Moreover, PEGMa was added again in the emulsion polymerization process to elevate the photothermal efficiency, and the irradiation result indicated that the NCs could increase the temperature by 27 °C. The complex microgel integrates pH/temperature/photothermal triple response characteristics and exhibits huge potential for chemo-photothermal combination cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Estrogen has been suggested to play a protective role against airway inflammations, such as asthma. In these processes, the inflammasome nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) partly accounts for the activation of pro-inflammatory factors. The aim of the present study was to investigate whether NLRP3 was involved in the protective effect of estrogen against allergic airway inflammation. Methods: An ovariectomy was performed on female C57BL/6 mice; some were sham-operated (sham). We then sensitized and challenged them with ovalbumin (OVA) to establish an airway inflammation model. Meanwhile, some mice were treated with 17β-estradiol (E2) for 28 days. Results: The expression of NLRP3 inflammasome and its downstream products, caspase-1 and the pro-inflammatory cytokine interleukin (IL)-1β (IL-1β), increased concomitantly with OVA-challenged airway inflammation and decreased with the expression of estrogen receptor β (ERβ). In addition, treating ovariectomized (OVX) mice with E2 dramatically ameliorated airway inflammation via such mechanisms as leukocyte recruitment, mucus production, and secretion of pro-inflammatory cytokines other than IL-18 in bronchoalveolar lavage (BAL) fluid (BALF). Furthermore, E2 suppressed both the mRNA expression and protein expression of NLRP3, caspase-1, and IL-1β. In summary, our study showed that NLRP3 inflammasome activation and pro-inflammatory cytokine production markedly increased in OVA-induced airway inflammation, and E2 effectively abrogated such inflammation by regulating the activation of NLRP3., (© 2018 The Author(s).)

To investigate the spectrum and frequency of phenylalanine hydroxylase (PAH) gene mutations in phenylketonuria (PKU) patients in Xinjiang, China. Polymerase chain reaction (PCR), in combination with single-strand conformation polymorphism (SSCP) and DNA sequencing analyses were performed, to screen potential mutations in the PAH gene in 46 individual PKU patients. Direct DNA sequencing was used to analyze the all of the exons in the PAH gene, including the promoter and flanking intron regions, in another 15 PKU patients. Our results indicated that, 30 different mutation types were identified in all 122 PAH alleles, with the mutation detection rate of 78.7% (96/122). Four novel mutations, i.e., 5'-Flanking -626G>A, 5'-Flanking -480DelACT, S196fsX4, and IVS8+1G>C, were identified for the first time. Similar to other regions in North China, R243Q, EX6-96A>G, IVS4-1A>G, R111X, and Y356X were the most prevalent PAH mutations in PKU patients from Xinjiang. Additionally, common mutations showed different frequencies in Xinjiang, when compared to other areas. Furthermore, sixteen different PAH gene mutation types were identified for the first time in the minorities in Xinjiang. Distinctive mutation spectrum of PAH gene in PKU patients from Xinjiang were characterized, which may promote the construction of PAH gene mutation database and serve as valuable tools for genetic diagnosis and counseling, and prognostic evaluation for PKU cases in the local area.