Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

Background

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT).

Methods

The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis.

Principal Findings

Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum.

Conclusion

Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”.     

红凤菜新鲜茎叶中总黄酮提取物的LC-MS分析

红凤菜（Gynura bicolor DC.）为菊科（Compositae）菊三七属（Gynura Cass.）植物,别名血皮菜、观音菜、观音苋、紫背天葵等,主要分布于中国南方各地,全草均可入药[1];也可作为蔬菜食用,在国内多个地区均有栽培和销售。目前已知红凤菜含有黄酮类、酚性酸类、萜类、甾醇类、脂肪酸类、生物碱类及花青素类等[2-7]成分。由于黄酮类成分多具有保护心血管、抗肿瘤、抗糖尿病、抗氧化、抗炎和抗病毒等作用[8],因此对红凤菜中黄酮类成分的研究具有深度开发价值。     

Heat shock protein gp96 regulates Toll-like receptor 9 proteolytic processing and conformational stability

Nucleic acid-sensing Toll-like receptors (TLRs) initiate innate immune responses to foreign RNA and DNA, yet can detect and respond to host DNA. To avoid autoimmune pathologies, nucleic acid sensing TLRs are tightly regulated. TLR9 primarily resides in the endoplasmic reticulum, traffics to endosomes, is proteolytically processed and responds to DNA. The heat shock protein gp96 is one of several accessory proteins that regulate intracellular trafficking of TLR9. In the absence of gp96, TLR9 fails to exit the endoplasmic reticulum, and therefore gp96-deficient macrophages fail to respond to CpG DNA. However, absence of gp96 precludes studies on potential chaperoning functions of gp96 for TLR9. Here we demonstrate that pharmacologic interference with gp96 function inhibits TLR9 signaling. TLR9 remains associated with gp96 during intracellular trafficking, and gp96-specific inhibitors increase TLR9 sensitivity to proteolytic degradation. We propose that gp96 is critical for both TLR9 egress from the ER, and for protein conformational stability in the endosomal compartment. These studies highlight the importance of examining gp96-specific inhibitors for modulating TLR9 activation, and the treatment autoimmune diseases.     

不同灌溉量对内蒙古人工草地主要牧草产量和水分利用效率的影响

人工草地建设是缓解内蒙古地区草地生存压力的必要途径,而水分短缺是该区人工草地建设中牧草生长的主要限制因素,适量的人工补水以实现牧草的高产节水是解决这一问题的关键。以当地主要牧草冰草和紫花苜蓿为研究对象,开展单播和混播条件下不同灌溉量对牧草产量、光合性能和水分利用效率影响的对比试验。研究结果表明:(1)豆禾混播有利于提高冰草和紫花苜蓿的产量;(2)8月初现蕾期是冰草和紫花苜蓿收割的最佳季节,此时牧草产量最高;(3)灌溉量达到田间持水量的45%(包含降雨量在内的单位面积灌溉量在7月初达到903.8 m3/hm2,在8月初达到1812.4 m3/hm2)是牧草高产节水的最佳补水选择;(4)6—8月水分胁迫更有利于提高牧草的长期水分利用效率(long-term water use efficiency,WUEL),开花期后补水对提高牧草WUEL的作用开始显著;(5)在牧草产量最高的8月初水分胁迫更有利于提高牧草的瞬时水分利用效率(instantaneous water use efficiency,WUEI),而在7月初光照强烈、水分蒸发量大时,较多地补水更有利于提高牧草的WUEI。     

New insights into the role of mitochondrial dysfunction and protein aggregation in Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative movement disorder that affects increasing number of elderly in the world population. The disease is caused by a selective degeneration of dopaminergic neurons in the substantia nigra pars compacta with the molecular mechanism underlying this neurodegeneration still not fully understood. However, various studies have shown that mitochondrial dysfunction and abnormal protein aggregation are two of the major contributors for PD. In fact this notion has been supported by recent studies on genes that are linked to familial PD (FPD). For instance, FPD linked gene products such as PINK1 and parkin have been shown to play critical roles in the quality control of mitochondria, whereas α-synuclein has been found to be the major protein aggregates accumulated in PD patients. These findings suggest that further understanding of how dysfunction of these pathways in PD will help develop new approaches for the treatment of this neurodegenerative disorder.     

GLIPR-2的生物学特性及与疾病的关系

神经胶质瘤致病相关蛋白2(glioma pathogenesis-related protein 2,GLIPR-2)是CAP蛋白质超家族中的一种高尔基体膜蛋白,具有CAP保守结构域,在体内的分布具有一定的组织和细胞特异性,在免疫器官和肺脏中表达较高。GLIPR-2与细胞膜系统具有高度的亲和力,可能与十四酰基化有关。GLIPR-2在HSAB和紫外光作用下形成二聚体,且能与Caveolin-1相互作用。GLIPR-2与疾病也很相关,目前发现GLIPR-2能诱导肾脏上皮细胞发生上皮细胞间质转化(epithelial to mesenchymal transition,EMT)而参与肾脏纤维化。CAP家族的SCRIP-3和GLIPR-1与肿瘤关系密切,GLIPR-2与上述两个蛋白具有相似的保守结构域,因此GLIPR-2可能也与肿瘤有关。     

An optical material for the detection of trace S<Subscript>2</Subscript>O<Subscript>3</Subscript><Superscript>2−</Superscript> in milk based on a copper complex

A novel S₂O₃ ^2? luminescent sensor (Cu²⁺-p-CPIP) was developed and the presence of S₂O₃ ^2? caused an obvious fluorescence enhancement at 420 nm upon excitation at 330 nm, which could be distinguished with the naked eye under a UV lamp. Remarkably, the compound exhibited excellent selective and sensitive response to S₂O₃ ^2? over other common anions with a micromolar limit of detection (0.442 μM) in DMSO/H₂O (v/v, 1:1) buffer. The absorbance intensity and the color of Cu²⁺-p -CPIP solution changed gradually with the increase of S₂O₃ ^2? concentration. The proposed method was applied to the determination of S₂O₃ ^2? in milk samples and the recoveries were 97.5–105%. The preparation of Cu²⁺-p -CPIP exhibited the quick, simple and facile advantages. The results showed that Cu²⁺-p -CPIP can be a good candidate for simple, rapid and sensitive colorimetric detection of S₂O₃ ^2? in aqueous solution.