Severe pneumonia associated with sepsis-induced myopathy: one case report and literature review / 中国感染控制杂志

Clinical data of one patient with sepsis-induced myopathy (SIM) who was successfully treated were reviewed retrospectively, analysis was conducted combined with the relevant literatures. Patient was a middle-aged woman without underlying disease, she was admitted to hospital because of fever, cough, chest tightness and shortness of breath, during the treatment period, type II respiratory failure occurred repeatedly, and it was difficult in withdrawing respirator, patient was finally diagnosed with SIM. After anti-infective treatment and rehabilitation training, she was successfully withdrawn respirator, muscle strength was recovered. This case suggests that SIM can be completely cured through early identification, neuromuscular nutrition therapy, graded rehabilitation training and lung rehabilitation therapy.

Role of Endoplasmic Reticulum Stress in Silica-induced Apoptosis in RAW264.7 Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We investigated the role of endoplasmic reticulum stress (ERS) in silica-induced apoptosis in alveolar macrophages in vitro.</p><p><b>METHODS</b>RAW264.7 cells were incubated with 200 μg/mL silica for different time periods. Cell viability was assayed by the MTT assay. Cell apoptosis was evaluated by DAPI staining, flow cytometry analysis, and Western blot analysis of caspase-3. Morphological changes in the endoplasmic reticulum were observed by transmission electron microscopy. The expression of ERS markers binding protein (BiP) and CCAAT-enhancer-binding protein homologous protein (CHOP) was examined by Western blotting and real-time PCR. As an inhibitor of ERS, 4-phenylbutyric acid (4-PBA) was used in the experiments.</p><p><b>RESULTS</b>Silica exposure induced nuclear condensation and caspase-3 expression in RAW264.7 cells. The number of apoptotic cells increased after silica exposure in a time-dependent manner. Silica treatment induced expansion of the endoplasmic reticulum. In addition, the expression of BiP and CHOP increased in silica-stimulated cells. Furthermore, 4-PBA treatment inhibited silica-induced endoplasmic reticulum expansion and the expression of BiP and CHOP. Moreover, 4-PBA treatment attenuated nuclear condensation, reduced apoptotic cells, and downregulated caspase-3 expression in silica-stimulated cells.</p><p><b>CONCLUSION</b>Silica-induced ERS is involved in the apoptosis of alveolar macrophages.</p>

Transcriptional Factor Snail Mediates Epithelial-Mesenchymal Transition in Human Bronchial Epithelial Cells Induced by Silica / 生物医学与环境科学（英文）

Epithelial-mesenchymal transition (EMT) plays an important role in fibrotic diseases. We have previously showed that silica induces EMT in human bronchial epithelial cells (BECs); however, the underlying mechanism of silica-induced EMT is poorly understood. In the present study, we investigated the role of Snail in silica-induced EMT in human BECs in vitro. Human BECs were treated with silica at various concentrations and incubation times. Then MTT assay, western blot, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) transfection were performed. We found that silica increased the expression and DNA binding activity of Snail in human BECs. SNAI siRNA inhibited the silica-induced expression of Snail. Moreover, SNAI siRNA upregulated the expression of epithelial marker E-cadherin, but attenuated the expression of mesenchymal marker α-smooth muscle actin and vimentin in silica-stimulated cells. These results suggest that Snail mediates the silica-induced EMT in human BECs.

Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced Acute Lung Injury in Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.</p><p><b>METHODS</b>C57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.</p><p><b>RESULTS</b>The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.</p><p><b>CONCLUSIONS</b>This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.</p>

Interferon regulatory factor-1 mediates the release of high mobility group box-1 in endotoxemia in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The extracellular release of the danger signal high mobility group box-1 (HMGB1) has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release can lead to the identification of targets that may inhibit this process. The transcription factor interferon regulatory factor-1 (IRF-1) is an important mediator of innate immune responses and has been shown to participate in mortality associated with endotoxemia; however, its role in mediating the release of HMGB1 in these settings is unknown.</p><p><b>METHODS</b>Male IRF-1 knockout (KO) and age matched C57BL/6 wild type (WT) mice were given intraperitoneal (IP) injections of lipopolysaccharide (LPS). In some experiments, 96 hours survival rates were observed. In other experiments, mice were sacrificed 12 hours after LPS administration and sera were harvested for future analysis. In in vitro study, RAW 264.7 murine monocyte/macrophage-like cells or primary peritoneal macrophage obtained from IRF-1 KO and WT mice were cultured for LPS mediated HMGB1 release analysis. And the mechanism for HMGB1 release was analyzed by immune-precipitation.</p><p><b>RESULTS</b>IRF-1 KO mice experienced less mortality, and released less systemic HMGB1 compared to their WT counterparts. Exogenous administration of recombinant HMGB1 to IRF-1 KO mice returned the mortality rate to that seen originally in IRF-1 WT mice. Using cultures of peritoneal macrophages or RAW264.7 cells, in vitro LPS stimulation induced the release of HMGB1 in an IRF-1 dependent manner. And the janus associated kinase (JAK)-IRF-1 signal pathway appeared to participate in the signaling mechanisms of LPS-induced HMGB1 release by mediating acetylation of HMGB1.</p><p><b>CONCLUSION</b>IRF-1 plays a role in LPS induced release of HMGB1 and therefore may serve as a novel target in sepsis.</p>

Effect of xinglong pingchuan recipe on interleukin-5 and the inflammagen related to oxygen free radical in asthmatic mice / 中南大学学报(医学版)

OBJECTIVE@#To observe the effect of Xinglong Pingchuan recipe (XLPCR) on interleukin-5 (IL-5), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) in mouse asthma models, and to explore its mechanism in treating asthma.@*METHODS@#The mouse asthma models were established by sensitization and challenge with ovalbumin (OVA). The asthma model was treated with XLPCR. At last, the number of white blood cells and eosinophil was counted, and the concentrations of inflammation factors such as IL-5, SOD, GPx, and MDA in the serum or the lung tissue of each mouse were detected.@*RESULTS@#Compared with the asthmatic group, the number of eosinophil in the XLPCR group decreased significantly (P 0.05, respectively). On the other hand, the concentration of MDA in the XLPCR group was significantly lower than that of the asthmatic group (P < 0.05).@*CONCLUSION@#XLPCR might inhibit the airway inflammation by decreasing the IL-5 level and adjusting the balance of oxidants/antioxidants.