Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways

Microglial-mediated neuroinflammation has been established as playing a vital role in pathogenesis of neurodegenerative disorders. Thus, rational regulation of microglia functions to inhibit inflammation injury may be a logical and promising approach to neurodegenerative disease therapy. The purposes of the present study were to explore the neuroprotective effects and potential molecular mechanism of Schizandrin A (Sch A), a lignin compound isolated from Schisandra chinesnesis. Our observations showed that Sch A could significantly down-regulate the increased production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-6 induced by lipopolysaccharide (LPS) both in BV-2 cells and primary microglia cells. Moreover, Sch A exerted obvious neuroprotective effects against inflammatory injury in neurons when exposed to microglia-conditioned medium. Investigations of the mechanism showed the anti-inflammatory effect of Sch A involved the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression levels and inhibition of the LPS-induced TRAF6-IKKβ-NF-κB pathway. Furthermore, inhibition of Jak2-Stat3 pathway activation and Stat3 nuclear translocation also was observed. In conclusion, SchA can exert anti-inflammatory and neuroprotective effects by alleviating microglia-mediated neuroinflammation injury through inhibiting the TRAF6-IKKβ-NF-κB and Jak2-Stat3 signaling pathways.     

The Strength of Mechanical Forces Determines the Differentiation of Alveolar Epithelial Cells

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Mechanical Forces Program the Orientation of Cell Division during Airway Tube Morphogenesis

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海南岛热带天然针叶林主要树种的空间格局及关联性

天然针叶林在热带地区虽较为少见, 但其对维持热带地区的生物多样性和生境异质性具有特殊意义。在我国热带天然针叶林集中分布面积最大的海南霸王岭林区, 作者选择伴生阔叶树种优势度不同的两种典型南亚松(Pinus latteri)天然林(简称纯林和混交林), 采用点格局法分析了其林冠层、亚林层和林下层主要树种的空间分布格局及其关联性。结果表明: (1)纯林中林冠层的南亚松主要为聚集分布, 混交林中在较小尺度上为聚集分布, 在较大尺度上为随机分布。(2)纯林中亚林层树种在较小尺度上为聚集分布, 在较大尺度上为随机分布, 在混交林中主要为聚集分布。(3)纯林中林下层树种主要呈现为随机分布, 而在混交林中主要为聚集分布。(4)随着尺度的增加, 林冠层与其他两个层次的树种, 在纯林中表现出从空间无关联到正关联的变化趋势, 而在混交林中则表现出从空间无关联到负关联的变化趋势。(5)亚林层与林下层树种在各个尺度上都表现为空间正关联。由此可见, 热带天然针叶林中优势种南亚松对伴生阔叶树种的分布格局具有重要影响。     

Age-dependent changes of airway and lung parenchyma in C57BL/6J mice.

In the current study, we hypothesize that senescent-dependent changes between airway and lung parenchymal tissues of C57BL/6J (B6) mice are not synchronized with respect to altered lung mechanics. Furthermore, aging modifications in elastin fiber and collagen content of the airways and lung parenchyma are remodeling events that differ with time. To test these hypotheses, we performed quasi-static pressure-volume (PV) curves and impedance measurements of the respiratory system in 2-, 20-, and 26-mo-old B6 mice. From the PV curves, the lung volume at 30 cmH(2)O pressure (V(30)) and respiratory system compliance (Crs) were significantly (P < 0.01) increased between 2 and 20 mo of age, representing about 80-84% of the total increase that occurred between 2 and 26 mo of age. Senescent-dependent changes in tissue damping and tissue elastance were analogous to changes in V(30) and Crs; that is, a majority of the parenchymal alterations in the lung mechanics occurred between 2 and 20 mo of age. In contrast, significant decreases in airway resistance (R) occurred between 20 and 26 mo of age; that is, the decrease in R between 2 and 20 mo of age represented only 29% (P > 0.05) of total decrease occurring through 26 mo. Morphometric analysis of the elastic fiber content in lung parenchyma was significantly (P < 0.01) decreased between 2 and 20 mo of age. To the contrary, increased collagen content was significantly delayed until 26 mo of age (P < 0.01, 2 vs. 26 mo). In conclusion, our data demonstrate that senescent-dependent changes in airway and lung tissue mechanics are not synchronized in B6 mice. Moreover, the reduction in elastic fiber content with age is an early lung remodeling event, and the increased collagen content in the lung parenchyma occurs later in senescence.     

Global expression profiles from C57BL/6J and DBA/2J mouse lungs to determine aging-related genes.

This study identified gene expression profiles that provided evidence for genomic mechanisms underlying the pathophysiology of aging lung. Aging lungs from C57BL/6 (B6) and DBA/2 (D2) mouse strains differ in physiology and morphometry. Lungs were harvested from B6 mice at 2, 18, and 26 mo and from D2 mice at 2 and 18 mo of age. Purified RNA was subjected to oligonucleotide microarray analyses, and differential expression analyses were performed for comparison of various data sets. A significant majority of differentially expressed genes were upregulated with aging in both strains. Aging D2 lungs uniquely exhibited upregulation in stress-response genes including xenobiotic detoxification cascades. In contrast, aging B6 lungs showed downregulation of heat shock-response genes. Age-dependent downregulation of genes common to both B6 and D2 strains included several collagen genes (e.g., Col1a1 and Col3a1). There was a greater elastin gene (Eln) expression in D2 mice at 2 mo, and Eln was uniquely downregulated with age in this strain. The matrix metalloproteinase 14 gene (Mmp14), critical to alveolar structural integrity, was also downregulated with aging in D2 mice only. Several polymorphisms in the regulatory and untranslated regions of Mmp14 were identified between strains, suggesting that variation in Mmp14 gene regulation contributes to accelerated aging of lungs in D2 mice. In summary, lungs of B6 and D2 mice age with variable rates at the gene expression level, and these quantifiable genomic differences provide a template for understanding the variability in age-dependent changes in lung structure and function.     

Environmental filtering of species with different functional traits into plant assemblages across a tropical coniferous-broadleaved forest ecotone

Background and aims

Ecotones between coniferous and broadleaved forests in tropical regions are poorly understood. Our aim was to understand community assembly across the ecotones by integrating changes in both plant functional traits and environmental factors.

Methods

The coniferous, ecotone, and broadleaved zones along each of the 15 investigation transects were discerned and surveyed. We measured eight functional traits of 174 woody species and 10 environmental factors along transects across the ecotones. We assessed between-site differences by using ANOVA, and correlations between functional traits and the environmental factors by RDA ordination.

Results

With the variation of vegetation zones from coniferous through the ecotone to broadleaved, the functional traits of plants at the community level changed in accordance with the changes in soil and light regimes. The low soil nutrients and low soil water in the coniferous zone were the major constraints for most lowland rain forest species with acquisitive traits, while high soil nutrients, high soil water and low light in the broadleaved zone had strong filtering effects on the conifer and tropical monsoon rainforest species with conservative traits.

Conclusions

The soil and light conditions were the major determinants for the functional community structure of the vegetation types across the tropical coniferous and broadleaved forest ecotone.     

Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice

Background

CD8+ T cells participate in airway hyperresponsiveness (AHR) and allergic pulmonary inflammation that are characteristics of asthma. CXCL10 by binding to CXCR3 expressed preferentially on activated CD8+ T cells, attracts T cells homing to the lung. We studied the contribution and limitation of CXCR3 to AHR and airway inflammation induced by ovalbumin (OVA) using CXCR3 knockout (KO) mice.

Methods

Mice were sensitized and challenged with OVA. Lung histopathological changes, AHR, cellular composition and levels of inflammatory mediators in bronchoalveolar lavage (BAL) fluid, and lungs at mRNA and protein levels, were compared between CXCR3 KO mice and wild type (WT) mice.

Results

Compared with the WT controls, CXCR3 KO mice showed less OVA-induced infiltration of inflammatory cells around airways and vessels, and less mucus production. CXCR3 KO mice failed to develop significant AHR. They also demonstrated significantly fewer CD8+ T and CD4+ T cells in BAL fluid, lower levels of TNFα and IL-4 in lung tissue measured by real-time RT-PCR and in BAL fluid by ELISA, with significant elevation of IFNγ mRNA and protein expression levels.

Conclusions

We conclude that CXCR3 is crucial for AHR and airway inflammation by promoting recruitment of more CD8+ T cells, as well as CD4+ T cells, and initiating release of proinflammatory mediators following OVA sensitization and challenge. CXCR3 may represent a novel therapeutic target for asthma.     

河蚌培养组织的几种生化成分分析

本文分析测定了三角帆蚌，褶纹冠蚌和背角无齿蚌外套膜培养组织及其培养液中的氨基酸，牛磺酸及钙含量。在珍蛛中含量较高的丙的氨酸和甘氨酸分别增加５４１％和９１％。三种蚌在培养中牛磺酸含量增加５．７８％到３倍，培养组织的钙含量增加１倍左右。同时测定了培养组织的碱性磷酸酶活性，培养组织与河蚌外套膜具有相近的比活及相对酶活。结果表明，河蚌外套膜在离体培养条件下，也具有分泌珍珠质的能力。     

背角无齿蚌碱性磷酸酶的功能基团研究

在一定条件下分别采用PMSF、DTT、PCMB、NBS、TNBS、SUAN、BrAc及IBr等化学修饰剂选择修饰背角无齿蚌碱性磷酸酶的多种氨基酸残基,并测定其酶活力变化。结果表明,PMSF、NBS、TNBS、SUAN、DTT的修饰能显著抑制酶的活力,活力的降低与修饰剂的浓度相关。BrAc、IAc、PCMB的修饰不表现对酶的抑制作用。作者初步认为,Ser、Lys和Trp残基是背角无齿蚌碱性磷酸酶的必需功能基团,部分二硫键时保护酶的催化功能也是必需的。