Background Muscle atrophy and weakness are adverse effects of high dose or the sustained usage of glucocorticoids. Loss of mitochondria and degradation of protein are highly correlated with muscle dysfunction. The deacetylase sirtuin 1 (SIRT1) plays a vital role in muscle remodelling. The current study was designed to identify myricanol as a SIRT1 activator, which could protect skeletal muscle against dexamethasone‐induced wasting. Methods The dexamethasone‐induced atrophy in C2C12 myotubes was evaluated by expression of myosin heavy chain, muscle atrophy F‐box (atrogin‐1), and muscle ring finger 1 (MuRF1), using western blots. The mitochondrial content and oxygen consumption were assessed by MitoTracker staining and extracellular flux analysis, respectively. Muscle dysfunction was established in male C57BL/6 mice (8–10 weeks old, n = 6) treated with a relatively high dose of dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, forced swimming capacity, muscle weight, and muscle histology were assessed. The expression of proteolysis‐related, autophagy‐related, apoptosis‐related, and mitochondria‐related proteins was analysed by western blots or immunoprecipitation. Results Myricanol (10 μM) was found to rescue dexamethasone‐induced muscle atrophy and dysfunction in C2C12 myotubes, indicated by increased expression of myosin heavy chain (0.33 ± 0.14 vs. 0.89 ± 0.21, * P < 0.05), decreased expression of atrogin‐1 (2.31 ± 0.67 vs. 1.53 ± 0.25, * P < 0.05) and MuRF1 (1.55 ± 0.08 vs. 0.99 ± 0.12, ** P < 0.01), and elevated ATP production (3.83 ± 0.46 vs. 5.84 ± 0.79 nM/mg protein, ** P < 0.01), mitochondrial content (68.12 ± 10.07% vs. 116.38 ± 5.12%, * P < 0.05), and mitochondrial oxygen consumption (166.59 ± 22.89 vs. 223.77 ± 22.59 pmol/min, ** P < 0.01). Myricanol directly binds and activates SIRT1, with binding energy of −5.87 kcal/mol. Through activating SIRT1 deacetylation, myricanol inhibits forkhead box O 3a transcriptional activity to reduce protein degradation, induces autophagy to enhance degraded protein clearance, and increases peroxisome proliferator‐activated receptor γ coactivator‐1α activity to promote mitochondrial biogenesis. In dexamethasone‐induced muscle wasting C57BL/6 mice, 5 mg/kg myricanol treatment reduces the loss of muscle mass; the percentages of quadriceps and gastrocnemius muscle in myricanol‐treated mice are 1.36 ± 0.02% and 0.87 ± 0.08%, respectively (cf. 1.18 ± 0.06% and 0.78 ± 0.05% in dexamethasone‐treated mice, respectively). Myricanol also rescues dexamethasone‐induced muscle weakness, indicated by improved grip strength (70.90 ± 4.59 vs. 120.58 ± 7.93 g, ** P < 0.01) and prolonged swimming exhaustive time (48.80 ± 11.43 vs. 83.75 ± 15.19 s, **...

Background and Purpose Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate whether myricanol improves insulin sensitivity and alleviates adiposity through modulating skeletal muscle–adipose tissue crosstalk. Experimental Approach The therapeutic effect of myricanol was evaluated on palmitic acid (PA)‐treated C2C12 myotubes and high‐fat diet (HFD)‐fed mice. The crosstalk between myotubes and adipocytes was evaluated using Transwell assay. The cellular lipid content was examined by Nile red staining. The mitochondrial content was assessed by MitoTracker Green staining and citrate synthase activity, and the mitochondrial function was examined by Seahorse assay. Expression of mitochondria‐related and insulin signalling pathway proteins was analysed by Western blot, and the irisin level was determined by elisa kit. Key Results Myricanol increased mitochondrial quantity and function through activating AMP‐activated protein kinase, resulting in reduced lipid accumulation and enhanced insulin‐stimulated glucose uptake, in PA‐treated C2C12 myotubes. Furthermore, myricanol stimulated irisin production and secretion from myotubes to reduce lipid content in 3T3‐L1 adipocytes. In HFD‐fed mice, myricanol treatment alleviated adiposity and insulin resistance through enhancing lipid utilization and irisin production in skeletal muscle and inducing browning of inguinal fat. Conclusions and Implications Myricanol modulates skeletal muscle–adipose tissue crosstalk, to stimulate browning of adipose tissue and improve insulin sensitivity in skeletal muscle. Myricanol might be a potential candidate for treating insulin resistance and obesity.

Palythoa caribaeorum (class Anthozoa) is a zoanthid that together jellyfishes, hydra, and sea anemones, which are venomous and predatory, belongs to the Phyllum Cnidaria. The distinguished feature in these marine animals is the cnidocytes in the body tissues, responsible for toxin production and injection that are used majorly for prey capture and defense. With exception for other anthozoans, the toxin cocktails of zoanthids have been scarcely studied and are poorly known. Here, on the basis of the analysis of P. caribaeorum transcriptome, numerous predicted venom-featured polypeptides were identified including allergens, neurotoxins, membrane-active, and Kunitz-like peptides (PcKuz). The three predicted PcKuz isotoxins (1-3) were selected for functional studies. Through computational processing comprising structural phylogenetic analysis, molecular docking, and dynamics simulation, PcKuz3 was shown to be a potential voltage gated potassium-channel inhibitor. PcKuz3 fitted well as new functional Kunitz-type toxins with strong antilocomotor activity as in vivo assessed in zebrafish larvae, with weak inhibitory effect toward proteases, as evaluated in vitro. Notably, PcKuz3 can suppress, at low concentration, the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish, which indicated PcKuz3 may have a neuroprotective effect. Taken together, PcKuz3 figures as a novel neurotoxin structure, which differs from known homologous peptides expressed in sea anemone. Moreover, the novel PcKuz3 provides an insightful hint for biodrug development for prospective neurodegenerative disease treatment.

Actinomycetes are a heterogeneous group of gram positive filamentous bacteria that have been found to produce a wide range of valuable bioactive secondary metabolites, particularly antibiotics. Moreover, actinomycetes isolated from unexplored environments show an unprecedented potential to generate novel active compounds. Hence, in order to search for novel antibiotics, we isolated and characterized actinomycetes strains from plant samples collected from a mangrove in Macau. Within the class of actinobacteria, fourteen actinomycetes isolates have been isolated and identified belonging to the genus of Streptomyces, Micromonospora, Mycobacterium, Brevibacterium, Curtobacterium and Kineococcus based on their 16S rRNA sequences. Further whole genome sequencing analysis of one of the isolated Streptomyces sp., which presented 99.13% sequence similarity with Streptomyces parvulus strain 2297, showed that it consisted of 118 scaffolds, 8,348,559 base pairs and had a 72.28% G + C content. In addition, genome-mining revealed that the isolated Streptomyces sp. contains 109 gene clusters responsible for the biosynthesis of known and/or novel secondary metabolites, including different types of terpene, T1pks, T2pks, T3pks, Nrps, indole, siderophore, bacteriocin, thiopeptide, phosphonate, lanthipeptide, ectoine, butyrolactone, T3pks-Nrps, and T1pks-Nrps. Meanwhile, the small molecules present in ethyl acetate extract of the fermentation broth of this strain were analyzed by LC-MS. Predicted secondary metabolites of melanin and desferrioxamine B were identified and both of them were firstly found to be produced by the Streptomyces parvulus strain. Our study highlights that combining genome mining is an efficient method to detect potentially promising natural products from mangrove-derived actinomycetes.

Long non-coding RNAs (lncRNAs) have been shown to play regulatory roles in a diverse range of biological processes and are associated with the outcomes of various diseases. The majority of studies about lncRNAs focus on model organisms, with lessened investigation in non-model organisms to date. Herein, we have undertaken an investigation on lncRNA in two zoanthids (cnidarian): Protolpalythoa varibilis and Palythoa caribaeorum. A total of 11,206 and 13,240 lncRNAs were detected in P. variabilis and P. caribaeorum transcriptome, respectively. Comparison using NONCODE database indicated that the majority of these lncRNAs is taxonomically species-restricted with no identifiable orthologs. Even so, we found cases in which short regions of P. caribaeorum’s lncRNAs were similar to vertebrate species’ lncRNAs, and could be associated with lncRNA conserved regulatory functions. Consequently, some high-confidence lncRNA-mRNA interactions were predicted based on such conserved regions, therefore revealing possible involvement of lncRNAs in posttranscriptional processing and regulation in anthozoans. Moreover, investigation of differentially expressed lncRNAs, in healthy colonies and colonial individuals undergoing natural bleaching, indicated that some up-regulated lncRNAs in P. caribaeorum could posttranscriptionally regulate the mRNAs encoding proteins of Ras-mediated signal transduction pathway and components of innate immune-system, which could contribute to the molecular response of coral bleaching.