Cachexia and muscle atrophy are common consequences of cancer chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake direct effects on proteolysis protein synthesis likely to mediate these effects, but the pathways leading events not well understood.We characterized molecular involved induced by Lewis lung carcinoma (LLC) tumour implantation c57/bl6 adult male mice administration chemotherapeutic agent cisplatin...

Expression, modification, and activity of microRNAs are dynamically regulated in early mouse embryos unveiled by sensitive sequencing.

Abstract Many positive signalling pathways of osteoclastogenesis have been characterized, but negative are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit α13 (Gα13) is a regulator osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice severe osteoporosis phenotype. -deficiency triggers drastic increase in both osteoclast number activity (hyper-activation), mechanistically through decreased RhoA enhanced...

Abstract Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering drug discovery, of which cysteine‐specific modification strategies are prominent inherent nucleophilicity low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives achieve multifaceted bioconjugation targeting cysteine‐containing peptides proteins. On one hand, this represents an...

Late-stage specific and selective diversifications of peptides proteins performed at target residues under ambient conditions are recognized to be the most facile route various abundant conjugates. Herein, we report an orthogonal modification cysteine using alkyl thianthreium salts, which proceeds with excellent chemoselectivity compatibility mild conditions, introducing a diverse array functional structures. Crucially, multifaceted bioconjugation is achieved through clickable handles...

An unprecedented tertiary amine catalyzed peptide allylation between Trp and MBH carbonates was disclosed, to enable late-stage functionalization macrocyclization both in traditional homogeneous phase on-resins SPPS.

The human protein C23 (nucleolin) is a major nucleolar protein. Its interactions with other proteins were studied the two‐hybrid system which identified B23 (nucleophosmin) as being associated C23. Both co‐immunoprecipitated from HeLa cell nuclear extract by either monoclonal anti‐C23 or anti‐B23. Binding studies utilizing deletion mutants indicated that binding of and involves specific motifs. In addition to an approximately 46‐amino‐acid‐binding domain in (amino acids 194–239), amino...

Skeletal muscle atrophy and weakness are thought to be stimulated by tumor necrosis factor α (TNF-α) in a variety of chronic diseases. However, little is known about the direct effects TNF-α on differentiated skeletal cells or signaling mechanisms involved. We have tested mouse-derived C2C12 cell line primary cultures from rat muscle. treatment myotubes time- concentration-dependent reductions total protein content loss adult myosin heavy chain (MHCf) content; these changes were evident at...

Abstract An efficient process involving the catalytic kinetic resolution of racemic spiro‐epoxyoxindoles with simultaneous enantioselective Friedel–Crafts alkylation indoles has been realized using a chiral phosphoric acid catalyst. The reaction provides two useful intermediates in high yields and excellent enantioselectivities. Performing catalysis on gram scale led to (R)‐3‐(3‐indolyl)‐oxindole‐3‐methanol, which was used asymmetric formal total synthesis (+)‐gliocladin C. Notably,...

Abstract Background Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to atrophy because increased protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB‐activated catabolism is poorly defined. Methods We investigated role p38β mitogen‐activated kinases (MAPK) mediating ActRIIB ligand A‐activated catabolic pathways C2C12 myotubes and mice with perturbation this kinase pharmacologically genetically. Results Treatment A or myostatin...

A method for introducing a range of phosphonates into oligopeptides through Michael addition reaction between dehydroalanine and phosphite is presented. The offers mild, cheap, straightforward approach to peptide phosphorylation that has potential applications in chemical biology medicinal chemistry. Moreover, the introduction phosphonate group short antibacterial peptides described demonstrate its utility, leading discovery phosphonated with potent broad-spectrum activity.

Abstract A gene encoding a possible novel human cathepsin, cysteine proteinase that is distinct from previously characterized enzymes, has been identified by differential screening of osteoclastoma cDNA library. This molecule, termed cathepsin X, appears to represent the homolog osteoclast-expressed rabbit OC-2. Cathepsin X (GenBank accession number U20280) 93.9% identical OC-2 at amino acid level, and 92% nucleotide level within coding region. 52.2 46.9% cathepsins S L, respectively,...

Abstract Because elevated ubiquitin ligase atrogin‐1/MAFbx and MuRF1 mediate skeletal muscle wasting associated with various catabolic conditions, the signaling pathways involved in upregulation of these genes under pathological conditions are considered therapeutic targets. AKT NF‐κB have been previously shown to regulate expression or MuRF1, respectively. In addition, we recently found that p38 MAPK mediates TNF‐α expression, suggesting multiple inflammatory diseases. To date, however,...

Grapholita molesta (Busck) is a worldwide insect pest damaging stone and pome fruits. High temperature can significantly affect survival, development fecundity. Heat shock protein (Hsp) genes were speculated to possess pivotal function in response high stress. In this study, two full-length Hsp genes, Gmhsp90 Gmhsp70, cloned from G. using rapid amplification of complementary DNA ends (RACE). The open reading frames Gmhsp70 obtained 2 148 bp 1 998 length, respectively. Their deduced amino...

A highly enantioselective oxidative dearomatization of naphthols with quinones catalyzed by a chiral spirocyclic phosphoric acid is described. The strategy provides concise access to enantioenriched cyclohexadienones quinone moiety. Remarkably, the obtained products could be easily transformed potentially useful dihydronaphtho[2,1-b]benzofuran scaffold.

Switching the chemo- or regioselectivity from identical starting materials under readily tunable reaction conditions represents a great challenge in medicinal and synthetic organic chemistry. Herein, we report asymmetric dearomatization/oxa-Michael Friedel–Crafts alkylation of 1-naphthols at C4 position, wherein chemoselectivity could be switched easily by using different without changing catalyst substrates. The reactions feature position dearomatization specific substrates stepwise protocols.

Many studies have shown effective protection from myocardial ischemia-reperfusion injury (MIRI) in animal models, but few, if any, treatments yielded a substantial reduction clinical. Several showed significant therapeutic effects for the Chinese patent medicine Suxiao Jiuxin Pill (SJP) MIRI, although specific molecular mechanisms remain undefined. Recently, increasing evidence indicates an important role m6A modification autophagy regulation and SJP has not been investigated this regard.In...