The critical role played by endotoxin-induced liver autophagy in the maintenance of lipid metabolism during sepsis

Macroautophagy/autophagy is a central mechanism by which cells maintain integrity and homeostasis, and endotoxin-induced autophagy plays important roles in innate immunity. Although TLR4 stimulation mediated by lipopolysaccharide (LPS) also upregulates autophagy in hepatocytes and liver, its physiological role remains elusive. The objective of this study was to determine the role of LPS-induced autophagy in the regulation of liver lipid metabolism. LPS treatment (5 mg/kg) increased autophagy, as detected by LC3 conversion and transmission electron microscopy (TEM) analysis in C57BL6 mouse livers. AC2F hepatocytes also showed increased autophagic flux after LPS treatment (1 μg/ml). To investigate the role of LPS-induced autophagy further, liver lipid metabolism changes in LPS-treated mice and fasted controls were compared. Interestingly, LPS-treated mice showed less lipid accumulation in liver than fasted mice despite increased fatty acid uptake and lipid synthesis-associated genes. In vitro analysis using AC2F hepatocytes demonstrated LPS-induced autophagy influenced the degradation of lipid droplets. Inhibition of LPS-induced autophagy using bafilomycin A₁ or Atg7 knockdown significantly increased lipid accumulation in AC2F hepatocytes. In addition, pretreatment with chloroquine aggravated LPS-induced lipid accumulation and inflammation in C57BL6 mouse livers. The physiological importance of autophagy was verified in LPS-treated young and aged rats. Autophagic response was diminished in LPS-treated aged rats and lipid metabolism was impaired during sepsis, indicating autophagy response is important for regulating lipid metabolism after endotoxin challenge. Our findings demonstrate endotoxin-induced autophagy is important for the regulation of lipid metabolism, and suggest that autophagy helps maintain lipid metabolism homeostasis during sepsis.     

Evaluation of the Microcirculation in a Rabbit Hemorrhagic Shock Model Using Laser Doppler Imaging

The aim of this study is to evaluate the feasibility of Laser Doppler imaging (LDI) for noninvasive and dynamic assessment of hemorrhagic shock in a rabbit model. A rabbit model of hemorrhagic shock was generated and LDI of the microcirculation in the rabbit ears was performed before and at 0, 30, 60, and 90 min after hemorrhage. The CCD (Charge Coupled Device) image of the ears, the mean arterial pressure (MAP) and the heart rate (HR) were monitored. The mean LDI flux was calculated. The HR of rabbits was significantly (p < 0.05) elevated and the MAP was decreased after hemorrhage, compared to the pre-hemorrhage level. Within the initial 30 min after hemorrhage, the perfusion flux lineally dropped down. In contrast, the MAP values did not differ significantly between the time points of 0 and 30 after hemorrhage (p > 0.05). Both the flux numbers and the red-to-blue color changes on LDI imaging showed the reduction of the microcirculation. LDI imaging is a noninvasive and non-contact approach to evaluate the microcirculation and may offer benefits in the diagnosis and treatment of hemorrhage shock. Further studies are needed to confirm its effectiveness in clinical practice.     

Anti-ultraviolet radiation effects of Coptis chinensis and Phellodendron amurense glycans by immunomodulating and inhibiting oxidative injury

HPLC analysis proved that Coptis chinensis glycan contained Ara, Man, and Gal. The monosaccharide constituents of Phellodendron amurense glycan were determined by HPLC analysis. HPLC analysis proved that P. amurense glycan contained Ara, Xyl, Glu, and Gal. FT-IR spectrum of C. chinensis glycan and P. amurense glycan showed the characteristic absorption peaks of carbohydrate polymers. Exposure of the human skin to ultraviolet radiation (UVR) leads to depletion of cutaneous antioxidants, regulation of gene expression and ultimately to the development of skin diseases. In the present study, free radical scavenging activity of C. chinensis and P. amurense glycan were evaluated. The photoprotective effect of C. chinensis and P. amurense glycan against UV-induced oxidative damage was also investigated in skin. At the concentration range employed, the two glycans showed strong free radical scavenging activity. Ultraviolet radiation reduced skin antioxidant enzyme and immunity activities in animals. Administration of C. chinensis and P. amurense glycans dose-dependently significantly increased skin antioxidant enzyme and immunity activities in animals. In conclusion, C. chinensis and P. amurense glycans present photoprotective properties, which can be attributed to molecules, such as flavonoids and carotenoids, which act as UV-absorbing molecules and as antioxidants, as well as stimulate immunity activities in animals.     

Ecological characteristics of plant species and associations along two Dinaric karstic rivers (Bosnia and Herzegovina, the Balkans)

This paper describes the plant communities of two oligotrophic karstic rivers with a slight anthropogenic influence — the Trebi?at and the Li?tica — in South Bosnia and Herzegovina, their sinecology, and the relationship between vegetation and plant species and environmental parameters. According to 87 relevés, a total of 26 plant associations, using Braun-Blanquet methods, were found in the rivers and nearby surveyed area. Only nine associations were common to both rivers. Eight associations were recorded for the territory of Bosnia and Herzegovina for the first time. Associations from both rivers differed according to following parameters measured at the sampling site: water temperature, distance from the mouth (river kilometers), river width, water depth, flow, pH and slope. There were no differences in nutrient concentrations among the associations. According to Canonical Correspondence Analysis (CCA), three environmental variables out of the 11 initially considered were retained as being related to plant distribution. The first two axes explained 56.8% and 35.2% of variance of species-environment relationship in the Trebi?at and Li?tica rivers, respectively. Water depth in the Trebi?at River, and pH and river kilometers in the Li?tica River were found to be the most influential, while nutrients and other physico-chemical parameters were not significant in either river. Water depth vector was identified as an underlying environmental factor determining distribution of Potamogeton lucens and Myriophyllum verticillatum (Potamion), and Nymphaea alba (Nymphaeion albae). According to in situ measurements of light intensity, the highest coefficients of light attenuation, radiance and reflection were found at a station with dense populations of Potamogeton lucens and Nuphar luteum (Potametum lucentis). The vegetation and floristic value of the rivers is discussed as a basis for biodiversity conservation programmes and evaluating the state of these ecosystems in the future.     

Dual targets for mouse mast cell protease-4 in mediating tissue damage in experimental bullous pemphigoid

Mouse mast cell protease-4 (mMCP-4) has been linked to autoimmune and inflammatory diseases, although the exact mechanisms underlying its role in these pathological conditions remain unclear. Here, we have found that mMCP-4 is critical in a mouse model of the autoimmune skin blistering disease bullous pemphigoid (BP). Mice lacking mMCP-4 were resistant to experimental BP. Complement activation, mast cell (MC) degranulation, and the early phase of neutrophil (PMN) recruitment occurred comparably in mMCP-4(-/-) and WT mice. However, without mMCP-4, activation of matrix metalloproteinase (MMP)-9 was impaired in cultured mMCP-4(-/-) MCs and in the skin of pathogenic IgG-injected mMCP-4(-/-) mice. MMP-9 activation was not fully restored by local reconstitution with WT or mMCP-4(-/-) PMNs. Local reconstitution with mMCP-4(+/+) MCs, but not with mMCP-4(-/-) MCs, restored blistering, MMP-9 activation, and PMN recruitment in mMCP-4(-/-) mice. mMCP-4 also degraded the hemidesmosomal transmembrane protein BP180 both in the skin and in vitro. These results demonstrate that mMCP-4 plays two different roles in the pathogenesis of experimental BP, by both activating MMP-9 and by cleaving BP180, leading to injury of the hemidesmosomes and extracellular matrix of the basement membrane zone.     

Spatial phylogenetics of the Chinese angiosperm flora provides insights into endemism and conservation

The flora of China is well known for its high diversity and endemism. Identifying centers of endemism and designating conservation priorities are essential goals for biodiversity studies.However, there is no comprehensive study from a rigorous phylogenetic perspective to understand patterns of diversity and endemism and to guide biodiversity conservation in China. We conducted a spatial phylogenetic analysis of the Chinese angiosperm flora at the generic level to identify centers of neo-and pale...     

Zn对细胞保护作用机理的研究

应用扫描质子微探针和同步辐射ｘ荧光分析技术测定了细胞中元素的分布和组成,为确定Zn是细胞结构成分提供了直接的实验依据.用上述核技术结合有关生化指标,分析测定了正常和损伤细胞（脂质过氧化损伤）中Fe,Zn和丙二醛、SH基含量变化的相互关系.实验结果表明,当细胞发生脂质过氧化损伤时,Fe含量和丙二醛含量同步增高,而Zn含量和SH基量则降低.给细胞补充Zn后,提高了细胞质膜中的Zn含量,SH基量也随之增加,同时丙二醛量降低.提示Zn保护细胞完整性的作用机理之一是控制脂质过氧化作用.Zn可保护膜蛋白的SH基,减少和阻止被Fe所催化的过氧化反应.