Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments

Background

Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.

Methodology/Principal Findings

We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C^hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.

Conclusions/Significance

The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.     

Shift in competitive ability mediated by soil biota in an invasive plant

Understanding the shifts in competitive ability and its driving forces is key to predict the future of plant invasion. Changes in the competition environment and soil biota are two selective forces that impose remarkable influences on competitive ability. By far, evidence of the interactive effects of competition environment and soil biota on competitive ability of invasive species is rare. Here, we investigated their interactive effects using an invasive perennial vine, Mikania micrantha. The competitive performance of seven M. micrantha populations varying in their conspecific and heterospecific abundance were monitored in a greenhouse experiment, by manipulating soil biota (live and sterilized) and competition conditions (competition‐free, intraspecific, and interspecific competition). Our results showed that with increasing conspecific abundance and decreasing heterospecific abundance, (1) M. micrantha increased intraspecific competition tolerance and intra‐ vs. interspecific competitive ability but decreased interspecific competition tolerance; (2) M. micrantha increased tolerance of the negative soil biota effect; and (3) interspecific competition tolerance of M. micrantha was increasingly suppressed by the presence of soil biota, but intraspecific competition tolerance was less affected. These results highlight the importance of the soil biota effect on the evolution of competitive ability during the invasion process. To better control M. micrantha invasion, our results imply that introduction of competition‐tolerant native plants that align with conservation priorities may be effective where M. micrantha populations are long‐established and inferior in inter‐ vs. intraspecific competitive ability, whereas eradication may be effective where populations are newly invaded and fast‐growing.     

人心肌肌球蛋白轻链1的克隆,表达纯化和单抗制备

报道了中国人心肌肌球蛋白轻链１ｃＤＮＡ的核苷酸序列,并由此推算的氨基酸序列。与国外发表的人心肌肌球蛋白轻链的氨基酸序列比较,发现有两处差异,即在２４位,由谷氨酸变为丙氨酸,则从９８位起至１０１位有４个氨基酸序列的连续差异,即由天冬酰胺－精氨酸－丝氨酸－赖氨酸变为赖氨酸－脯氨酸－精氨酸－谷氨酰妥,推测可能是由于人种差异而引起的。利用该ｃＤＮＡ在大肠杆菌内的表达产物,已获得一株高效的抗中国人心肌肌球蛋     

Effects of Different Sources and Levels of Copper on Growth Performance,Nutrient Digestibility,and Elemental Balance in Young Female Mink (Mustela vison)

An experiment was conducted in a 3?×?3?+?1 factorial experiment based on a completely randomized design to evaluate the effects of different sources of copper on growth performance, nutrient digestibility and elemental balance in young female mink on a corn–fishmeal-based diet. Animals in the control group were fed a basal diet (containing 8.05 mg Cu/kg DM; control), which mainly consisted of corn, fish meal, meat bone meal, and soybean oil, with no copper supplementation. Minks in other nine treatments were fed basal diets supplemented with Cu from reagent-grade copper sulfate, tribasic copper chloride (TBCC) and copper methionate. Cu concentrations of experiment diets were 10, 25, and 40 mg/kg copper. A metabolism trial of 4 days was conducted during the last week of experimental feeding. Final body weight and average daily gain increased (linear and quadratic, P?<?0.05) as Cu increased in the diet; maximal growth was seen in the Cu25 group. Cu supplementation slightly improved the feed conversion rate (P?=?0.095). Apparent fat digestibility was increased by copper level (P?=?0.020). Retention nitrogen was increased by copper level (linear, P?=?0.003). Copper source had a significant effect on copper retention with Cu-Met and copper sulfate treatments retention more than TBCC treatments (P?<?0.05). Our results indicate that mink can efficiently utilize added dietary fat and that Cu plays an important role in the digestion of dietary fat in mink, and mink can efficiently utilize Cu-Met and CuSO₄.     

The role of Ca2+/Calcineurin/NFAT signalling pathway in osteoblastogenesis

The bone remodelling process is closely related to bone health. Osteoblasts and osteoclasts participate in the bone remodelling process under the regulation of various factors inside and outside. Excessive activation of osteoclasts or lack of function of osteoblasts will cause occurrence and development of multiple bone‐related diseases. Ca²⁺/Calcineurin/NFAT signalling pathway regulates the growth and development of many types of cells, such as cardiomyocyte differentiation, angiogenesis, chondrogenesis, myogenesis, bone development and regeneration, etc. Some evidences indicate that this signalling pathway plays an extremely important role in bone formation and bone pathophysiologic changes. This review discusses the role of Ca²⁺/Calcineurin/NFAT signalling pathway in the process of osteogenic differentiation, as well as the influence of regulating each component in this signalling pathway on the differentiation and function of osteoblasts, whereby the relationship between Ca²⁺/Calcineurin/NFAT signalling pathway and osteoblastogenesis could be deeper understood.     

Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase

Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion.