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Background Cancer cachexia as a metabolic syndrome can lead to at least 25% of cancer deaths. The inhibition of muscle atrophy is a main strategy to treat cancer cachexia. In this process, myostatin (MSTN) can exert a dual effect on protein metabolism, including inhibition of protein biosynthesis and enhancement of protein degradation. In this study, we will test the effect on muscle atrophy induced by cancer cachexia of IMB0901, a MSTN inhibitor. Methods Two high-throughput screening models against MSTN were developed. By screening, IMB0901, 2-((1-(3,4-dichlorophenyl)-1H-pyrazolo [3,4-d] pyrimidin-4-yl) amino) butan-1-ol, was picked out from the compound library. The in vitro cell model and the C26 animal model of muscle atrophy induced by cancer cachexia were used to determine the pharmacological activity of IMB0901. Whether IMB0901 could inhibit the aggravating effect of doxorubicin on muscle wasting was examined in vitro and in vivo. Results IMB0901 inhibited the MSTN promoter activity, the MSTN signaling pathway, and the MSTN positive feedback regulation. In atrophied C2C12 myotubes, IMB0901 had a potent efficiency of decreasing MSTN expression and modulating MSTN signaling pathway which was activated by C26-conditioned medium (CM). In C2C12 myotubes, the expressions of three common myotube markers, myosin heavy chain (MyHC), myogenic differentiation 1 (MyoD), and myogenin (MyoG), were downregulated by CM, which could be efficiently reversed by IMB0901 via reduction of ubiquitin-mediated proteolysis and enhancement of AKT/mTOR-mediated protein synthesis. In the C26 animal model, IMB0901 mitigated the weight loss of body, quadricep and liver, and protected the quadriceps cell morphology. Furthermore, IMB0901 decreased the expression of two E3 ligases Atrogin-1 and MuRF-1 in the quadriceps in vivo. At the cellular level, IMB0901 had no influence on anti-tumor effect of three chemotherapeutic agents (cisplatin, doxorubicin, and gemcitabine) and lowered doxorubicin-induced upregulation of MSTN in C2C12 myotubes. IMB0901 did not affect the inhibitory effect of doxorubicin on C26 tumor and delayed the weight loss of muscle and adipose tissue caused by C26 tumor and doxorubicin. Conclusions IMB0901 inhibits muscle atrophy induced by cancer cachexia by suppressing ubiquitin-mediated proteolysis and promoting protein synthesis. These findings collectively suggest that IMB0901 is a promising leading compound for the management of muscle atrophy induced by cancer cachexia. Electronic supplementary material The online version of this article (10.1186/s13395-019-0193-2) contains supplementary material, which is available to authorized users.

Soil microbes play an important role in terrestrial carbon (C) cycling, but their functional response to global warming remains yet unclear. Soil metaproteomics has the potential to contribute to a better understanding of warming effects on soil microbes as proteins specifically represent active microbes and their physiological functioning. To quantify warming effects on microbial proteins and their distribution among different functional and phylogenetic groups, we sampled forest soil that had been artificially warmed (+4 °C) during seven consecutive growing seasons and analyzed its metaproteomic fingerprint and linked to soil respiration as a fundamental ecosystem service. Bacterial protein abundances largely exceeded fungal abundances at the study site but protein abundances showed only subtle differences among control and warmed soil at the phylum and class level, i.e. a temperature-induced decrease in Firmicutes , an increase in Agaricomycetes and Actinobacteria , and a decrease in the Asco/Basidiomycota ratio. Community function in warmed soil showed a clear trend towards increased proteins involved in microbial energy production and conversion, related to the increased CO 2 efflux from warmed soil as a result of stress environmental conditions. The differences in community function could be related to specific phyla using metaproteomics, indicating that microbial adaptation to long-term soil warming mainly changed microbial functions, which is related to enhanced soil respiration. The response of soil respiration to warming (+35% soil CO 2 efflux during sampling) has not changed over time. Accordingly, potential long-term microbial adaptations to soil warming were too subtle to affect soil respiration rates or, were overlaid by other co-varying factors (e.g. substrate availability).