Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury

Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia–reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI.     

糖原磷酸化酶BB在心脏直视手术后心肌损伤中的判定价值

目的:探讨糖原磷酸化酶BB对心脏直视手术后心肌损伤的判定价值.方法:108例行心脏瓣膜置换手术患者,分别于围术期多个时点取桡动脉血,测定血清糖原磷酸化酶BB、心肌肌钙蛋白I(cTnI)、肌酸磷酸激酶同工酶(CKMB)的水平,并检测心肌细胞凋亡程度.结果:血清糖原磷酸化酶BB于体外循环主动脉开放后最早达峰值,其峰值与cT...     

南沙群岛西南部和北部湾口海域鱼类物种多样性

根据2012-2013年在南沙群岛西南部和北部湾口海域春秋两个航次的调查资料, 分析了该海域鱼类种类组成、相对重要性指数和物种多样性等特征。结果表明, 两个航次调查共鉴定鱼类504种, 隶属于2纲31目129科294属; 其中北部湾口海域出现鱼类301种, 南沙群岛西南部海域出现鱼类357种。优势种数量较少, 多以中小型鱼类为主, 且季节间变化较大。春季多样性指数高于秋季, 这主要是因为春季出现的大量鱼类为补充群体, 而许多种类在秋季有向较深海区移动的趋势; 南沙群岛西南部海域多样性指数高于北部湾口海域, 这主要是由于南沙群岛西南部海域受水温和洋流的影响较大造成的。更替指数和迁移指数显示, 秋季鱼类群落结构稳定性要低于春季, 而且两个季节的鱼类群落结构都偏离平衡状态, 主要是由鱼类的洄游和不同适温性鱼类的迁入迁出造成的。综合来看, 南沙群岛西南部海域鱼类物种多样性和群落结构稳定性均高于北部湾口海域, 在努力控制资源可捕量范围的同时, 可合理开发南海中南部海域的渔业资源。     

Downregulation of microRNA-23b protects against ischemia-reperfusion injury via p53 signaling pathway by upregulating MDM4 in rats

Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia-reperfusion injury (IRI). More recently, microRNAs (miRs) have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA-23b (miR-23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR-23b, MDM4, and the p53 signaling pathway-related genes was characterized in cartilaginous tissues. Then, miR-23b mimics or inhibitors were applied for the elevation or the depletion of the miR-23b expression and siRNA-MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR-23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR-23b through. Downregulated miR-23b increased the expression of MDM4, AKT, and Bcl-2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR-23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR-23b was observed after MDM4 knocked down. Our results indicate that silencing miR-23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI.     

CD44 fucosylation on mesenchymal stem cell enhances homing and macrophage polarization in ischemic kidney injury

The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24 h after injury and reduced lung stasis. An in vitro adhesion assay revealed that transfection enhanced the association between MSCs and hypoxic endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at the renal capsule, and some MSCs later migrated inward between tubules. Most homing MSCs were in close contact with inflammatory cells without tubular transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated renal injury, partly by enhancing the polarization of infiltrating macrophages. In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection might enhance renotropism and the regenerating ability of MSCs in ischemic kidney injury.     

韭山列岛自然保护区虾类优势种生态位

根据韭山列岛自然保护区2015年11月, 2016年2月、5月、8月的调查资料, 运用相对重要性指数(index of relative importance, IRI)、生态位宽度以及生态位重叠指数等生态指标, 对调查海域的优势种虾类进行生态位特征分析, 以了解该海域内虾类组成及优势种间的关系。结果表明, 保护区共调查到虾类16种, 隶属8科12属, 均属暖温种或暖水种, 其中优势种(IRI > 500)有7种, 隶属于4科5属; 虾类相对资源量呈春秋季高, 夏冬季低的季节性分布特征。除脊尾白虾(Exopalaemon carinicauda)外, 优势种的时空生态位宽度值(时间生态位宽度与空间生态位宽度的乘积)均大于非优势种。日本鼓虾(Alpheus japonicus)和细巧仿对虾(Parapenaeopsis tenella)的时空二维生态位重叠值最大, 表明其对资源的利用具有相似性; 安氏白虾(Exopalaemon annandalei)和哈氏仿对虾(Parapenaeopsis hardwickii)的时空生态位重叠值最小, 说明二者相关性低。通过计算得知, 相对重要性指数(IRI)与生态位宽度对物种重要性排序结果有异: 时空生态位宽度值最大的为葛氏长臂虾(Palaemon gravieri), 而IRI值最高的为日本鼓虾。与相对重要性指数(IRI)相比, 生态位宽度指数不仅能反映物种对资源的利用能力, 还能反映物种分布是否均匀, 但这两者均不能反映生物量的多少。     

PGC‐1α protects from myocardial ischaemia‐reperfusion injury by regulating mitonuclear communication

The recovery of blood supply after a period of myocardial ischaemia does not restore the heart function and instead results in a serious dysfunction called myocardial ischaemia‐reperfusion injury (IRI), which involves several complex pathophysiological processes. Mitochondria have a wide range of functions in maintaining the cellular energy supply, cell signalling and programmed cell death. When mitochondrial function is insufficient or disordered, it may have adverse effects on myocardial ischaemia‐reperfusion and therefore mitochondrial dysfunction caused by oxidative stress a core molecular mechanism of IRI. Peroxisome proliferator‐activated receptor gamma co‐activator 1α (PGC‐1α) is an important antioxidant molecule found in mitochondria. However, its role in IRI has not yet been systematically summarized. In this review, we speculate the role of PGC‐1α as a key regulator of mitonuclear communication, which may interacts with nuclear factor, erythroid 2 like ‐1 and ‐2 (NRF‐1/2) to inhibit mitochondrial oxidative stress, promote the clearance of damaged mitochondria, enhance mitochondrial biogenesis, and reduce the burden of IRI.     

Carbohydrate structure and serological behaviour of "antifreeze" glycoproteins from an Antarctic fish.

The carbohydrate moiety of the “antifreeze” glycoprotein from $\text{Trematomus borchgrevinki}$ was found to be β-D-galactosyl 1–3 N-acetyl galactosamine by gasliquid chromatography. The glycoprotein inhibited anti-T antibody from human serum and $\text{Arachis hypogoea}$ lectin, but was inactive against $\text{Vicia graminea}$. Native “antifreeze” glycoprotein did not inhibit the agglutinins from $\text{Helix pomatia}$ or $\text{Cepaea hortensis}$, although after Smith degradation showed a strong inhibition towards them. Inhibition of the latter agglutinin demonstrates the carbohydrate-protein linkage to be α-linked. The presence of the Thomsen-Friedenreich antigen (T-antigen) on the “antifreeze” glycoprotein and its relation to tumour cell surfaces is briefly discussed.     

Studies on submaxillary gland immunoreactive glucagon.

Biologically active immunoreactive glucagon is present in submaxillary gland of rat, mouse, guinea pig and human and can be extracted by saline adjusted to pH 2.8 with HCl. Chromatography on Sephadex G-150 indicates its molecular weight to be 29,000. It has similar immunologic characteristics as pancreatic glucagon. It is biologically active and elevates plasma glucose and insulin when injected intraperitoneally into rats. Compared to pancreatic glucagon, the hyperglycemic effect persists much longer. It competes with pancreatic glucagon for binding to specific glucagon receptors of rat liver plasma membranes. It is stable to pH changes, however, urea dissociates it into several smaller molecular weight fragments including that of 3500. It appears to be an aggregate of smaller glucagon molecules and is not responsible for immunoreactive glucagon in totally eviscerated rats. $\text{In vitro}$, the submaxillary gland does not release immunoreactive glucagon in response to arginine or glucose.     

Proteome variation of the rat liver after static cold storage assayed in an ex vivo model

Cold storage is a common procedure for liver preservation in a transplant setting. However, during cold ischemia, the liver suffers molecular alterations that can affect its performance. Also, deleterious mechanisms set forth in the storage phase are exacerbated during reperfusion. This study aimed to identify liver proteins associated with injury during cold storage and/or normothermic reperfusion using the isolated perfused rat liver model. Livers from male rats were subjected to either (1) cold storage for 24 h, (2) ex vivo normothermic reperfusion for 90 min or (3) cold storage for 24 h followed by ex vivo normothermic reperfusion for 90 min. Then, the livers were homogenized and proteins were extracted. Protein expression between each experimental group and the control (freshly resected livers) was compared by two-dimensional (2D) gel electrophoresis. Protein identification was carried out by matrix‐assisted laser desorption/ionization time‐of‐flight spectrometry (MALDI‐TOF/TOF) using MASCOT as the search engine. 23 proteins were detected with significantly altered levels of expression among the different treatments, including molecular chaperones, antioxidant enzymes, and proteins involved in energy metabolism. Some of them have been postulated as biomarkers for liver damage while others had been identified in other organs subjected to ischemia and reperfusion injury. The whole data set will be a useful resource for studying deleterious molecular mechanisms that result in diminished liver function during storage and subsequent reperfusion.