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Objectives Investigating the antipulmonary fibrosis effect of mangiferin from Mangifera indica and the possible molecular mechanism. Methods In vivo, bleomycin (BLM)‐induced pulmonary fibrosis experimental model was used for evaluating antipulmonary fibrosis effect of mangiferin. Histopathologic examination and collagen deposition were investigated by HE and Masson staining as well as detecting the content of hydroxyproline. The expression of transforming growth factor‐β1 (TGF‐β1), α‐smooth muscle actin (α‐SMA), TLR4 and p‐P65 in lung tissue was analysed through immunofluorescence. Leucocytes and inflammatory cytokines including IL‐1β, IL‐6, TNF‐α and MCP‐1 in bronchoalveolar lavage fluid were detected by cell counting and enzyme‐linked immunosorbent assay. In vitro, TGF‐β1‐induced A549 epithelial–mesenchymal transition (EMT) cell model was used for investigating the possible molecular mechanism. Reactive oxygen species (ROS) generation was detected by DCFH‐DA assay. Expression of all proteins was examined by Western blot. Key findings Oral administration of mangiferin could attenuate the severity of BLM‐induced pulmonary fibrosis through increasing the survival rate, improving histopathological lesion and body weight loss as well as decreasing pulmonary index visibly. Pulmonary hydroxyproline content, TGF‐β1, and α‐SMA levels were reduced significantly. The molecular mechanism of mangiferin for inhibiting pulmonary fibrosis is that it could obviously inhibit the occurrence of inflammation and the secretion of inflammatory cytokine through inhibiting activation of TLR4 and phosphorylation of p65. Meanwhile, EMT process was suppressed obviously by mangiferin through blocking the phosphorylation of Smad2/3 and reducing MMP‐9 expression. Besides, mangiferin could significantly inhibit the process of oxidant stress through downregulating the intracellular ROS generation. Conclusions Mangiferin attenuates BLM‐induced pulmonary fibrosis in mice through inhibiting TLR4/p65 and TGF‐β1/Smad2/3 pathway.

In this paper, the transport of sub-cooled water across a partially frozen soil matrix (frozen fringe) caused by a temperature difference over the fringe, is described using non-equilibrium thermodynamics. A set of coupled transport equations of heat and mass is presented; implying that, in the frozen fringe, both driving forces of pressure and temperature gradients simultaneously contribute to transport of water and heat. The temperature-gradient-induced water flow is the main source of frost heave phenomenon that feeds the growing ice lens. It is shown that three measurable transport coefficients are adequate to model the process; permeability (also called hydraulic conductivity), thermal conductivity and a cross coupling coefficient that may be named thermodynamic frost heave coefficient. Thus, no ad hoc parameterizations are required. The definition and experimental determination of the transport coefficients are extensively discussed in the paper. The maximum pressure that is needed to stop the growth of an ice lens, called the maximum frost heave pressure, is predicted by the proposed model. Numerical results for corresponding temperature and pressure profiles are computed using available data sets from the literature. Frost heave rates are also computed and compared with the experimental results, and reasonable agreement is achieved.

ABSTRACT. We evaluated the potentially protective effect of nimodipine on rat spinal cord injury. Sprague-Dawley rats received spinal cord injury, and were separated into nimodipine (N = 12) and saline groups (N = 12). Within 1 h of the injury, rats were treated intraperitoneally with nimodipine (1.0 mg/kg) or an equal amount of saline. Treatment was performed 3 times a day for 1 week. Operation BBB score and track experiment were used to measure the physical function of the hind legs 1 and 2 weeks after injury. Two weeks after the injury, malondialdehyde (MDA) content and spinal cord myeloperoxidase (MPO) activity of the injured part were determined, and the glial scar and dead room were studied using the immune tissue chemical test. ED1 was used to observe active gitter cell and macrophages. The physical function of the nimodipine group improved significantly (P < 0.01). Two weeks after injury, spinal cord MDA content in the spinal cord in the nimodipine group (nmol/g, 25.6 ± 9.7 vs 68.5 ± 16.7) and MPO activity (U/g, 252.2 ± 63.9 vs 382.8 ± 108.2) decreased significantly (P < 0.01); nimodipine whole dead space (mm 2 , 4.45 ± 1.28 vs 6.16 ± 2.65) and ED1 antibody immunity colored positive room (mm 2 , 1.87 ± 0.42 vs 2.86 ± 1.01) reduced significantly 1270

BackgroundDuchenne muscular dystrophy caused by a mutation in the X-linked dystrophin gene induces metabolic and structural disorders in the brain. A lack of dystrophin in brain structures is involved in impaired cognitive function. Prosaposin (PS), a neurotrophic factor, is abundant in the choroid plexus and various brain regions. We investigated whether PS serves as a link between dystrophin loss and gross and/or ultrastructural brain abnormalities.Methodology/Principal FindingsThe distribution of PS in the brains of juvenile and adult mdx mice was investigated by immunochemistry, Western blotting, and in situ hybridization. Immunochemistry revealed lower levels of PS in the cytoplasm of neurons of the cerebral cortex, hippocampus, cerebellum, and choroid plexus in mdx mice. Western blotting confirmed that PS levels were lower in these brain regions in both juveniles and adults. Even with low PS production in the choroids plexus, there was no significant PS decrease in cerebrospinal fluid (CSF). In situ hybridization revealed that the primary form of PS mRNA in both normal and mdx mice was Pro+9, a secretory-type PS, and the hybridization signals for Pro+9 in the above-mentioned brain regions were weaker in mdx mice than in normal mice. We also investigated mitogen-activated protein kinase signalling. Stronger activation of ERK1/2 was observed in mdx mice, ERK1/2 activity was positively correlated with PS activity, and exogenous PS18 stimulated both p-ERK1/2 and PS in SH-SY5Y cells.Conclusions/SignificanceLow levels of PS and its receptors suggest the participation of PS in some pathological changes in the brains of mdx mice.