Sugammadex affects GH/GHR’s signaling transduction on muscle cells by regulating the membrane-localized GHR level

Objectives Sugammadex (also known as bridion) is a modified γ-cyclodextrin, which is a reversal agent for the neuromuscular block. Growth hormone (GH) has an important biological effect on muscle, regulating muscle growth and development. In the current work, we explored the effect of Sugammadex on GH’s bioactivities. Methods Confocal laser scanning microscope (CLSM), flow cytometry, indirect immunofluorescence, Western-blot, and IP-WB were used to explore the effect of Sugammadex on GH’s bioactivities. Results We found that Sugammadex reduced the activity of GH on muscle cells, which down-regulated GH/GHR-mediated intracellular signaling pathway, such as Janus kinase 2 (JAK2) and signal transducers and activators of transcription 5 (STAT5). We further study the potential biological mechanism by which Sugammadex down-regulated GH/GHR-mediated signaling pathway, a series of related experiments were conducted, and found that Sugammadex may inhibit the proliferation of C2C12 cell via regulating the membrane-localized GHR, which may be the underlying mechanism by which Sugammadex suppressed GHR-induced signaling transduction. This work has laid the theoretical and experimental basis for further exploring the relationship between Sugammadex and GH’s activity. Conclusions In conclusion, this study laid a foundation for further study on the relationship between Sugammadex and GH’s activity.

Nanopore-Based Comparative Transcriptome Analysis Reveals the Potential Mechanism of High-Temperature Tolerance in Cotton (Gossypium hirsutum L.)

Extreme high temperatures are threatening cotton production around the world due to the intensification of global warming. To cope with high-temperature stress, heat-tolerant cotton cultivars have been bred, but the heat-tolerant mechanism remains unclear. This study selected heat-tolerant (‘Xinluzao36′) and heat-sensitive (‘Che61-72′) cultivars of cotton treated with high-temperature stress as plant materials and performed comparative nanopore sequencing transcriptome analysis to reveal the potential heat-tolerant mechanism of cotton. Results showed that 120,605 nonredundant sequences were generated from the raw reads, and 78,601 genes were annotated. Differentially expressed gene (DEG) analysis showed that a total of 19,600 DEGs were screened; the DEGs involved in the ribosome, heat shock proteins, auxin and ethylene signaling transduction, and photosynthesis pathways may be attributed to the heat tolerance of the heat-tolerant cotton cultivar. This study also predicted a total of 5118 long non-coding RNAs (lncRNAs)and 24,462 corresponding target genes. Analysis of the target genes revealed that the expression of some ribosomal, heat shock, auxin and ethylene signaling transduction-related and photosynthetic proteins may be regulated by lncRNAs and further participate in the heat tolerance of cotton. This study deepens our understandings of the heat tolerance of cotton.

Transcriptome Reprogramming of Tomato Orchestrate the Hormone Signaling Network of Systemic Resistance Induced by Chaetomium globosum

Chaetomium globosum is a potential biological control agent effective against various plant pathogens. Several reports are available on the mycoparastism and antibiosis mechanisms of C. globosum against plant pathogenic fungi, whereas a few states induced resistance. The potential induced defense component of C. globosum (Cg-2) was evaluated against early blight disease of tomato (Solanum lycopersicum) and further, global RNA sequencing was performed to gain deep insight into its mechanism. The expression of marker genes of hormone signaling pathways, such as PR1, PiII, PS, PAL, Le4, and GluB were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR) to determine the best time point for RNA sequencing. The transcriptome data revealed that 22,473 differentially expressed genes (DEGs) were expressed in tomato at 12 h post Cg-2 inoculation as compared with control plants and among these 922 DEGs had a fold change of −2 to +2 with p < 0.05. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that most of the DEGs were belonging to metabolic pathways, biosynthesis of secondary metabolites, plant–pathogen interaction, chlorophyll metabolism, and plant hormone signal transduction. Gene Ontology (GO) analysis revealed that DEGs were enriched mainly related to binding activity (GO:0005488), catalytic activity (GO:0003824), metabolic process (GO:0008152), cellular process (GO:0009987), response to stimulus (GO:0050896), biological regulation (GO:0065007), and transcription regulator activity (GO:0140110). The gene modulations in hormone signaling transduction, phenylpropanoid biosynthesis, and mitogen-activated protein kinases (MPK) signaling indicated the upregulation of genes in these pathways. The results revealed active participation of jasmonic acid (JA) and salicylic acid (SA) signaling transduction pathways which further indicated the involvement of induced systemic resistance (ISR) and systemic acquired resistance (SAR) in the systemic resistance induced by Cg-2 in tomato.

4.1N-Mediated Interactions and Functions in Nerve System and Cancer

Scaffolding protein 4.1N is a neuron-enriched 4.1 homologue. 4.1N contains three conserved domains, including the N-terminal 4.1-ezrin-radixin-moesin (FERM) domain, internal spectrin–actin–binding (SAB) domain, and C-terminal domain (CTD). Interspersed between the three domains are nonconserved domains, including U1, U2, and U3. The role of 4.1N was first reported in the nerve system. Then, extensive studies reported the role of 4.1N in cancers and other diseases. 4.1N performs numerous vital functions in signaling transduction by interacting, locating, supporting, and coordinating different partners and is involved in the molecular pathogenesis of various diseases. In this review, recent studies on the interactions between 4.1N and its contactors (including the α7AChr, IP3R1, GluR1/4, GluK1/2/3, mGluR8, KCC2, D2/3Rs, CASK, NuMA, PIKE, IP6K2, CAM 1/3, βII spectrin, flotillin-1, pp1, and 14-3-3) and the 4.1N-related biological functions in the nerve system and cancers are specifically and comprehensively discussed. This review provides critical detailed mechanistic insights into the role of 4.1N in disease relationships.

Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s−1) and high (1800 s−1) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s−1). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.

Remodeling of ryanodine receptor isoform 1 channel regulates the sweet and umami perception of Rattus norvegicus

Sweet and umami are respectively elicited by sweet/umami receptor on the tongue and palate epithelium. However, the molecular machinery allowing to taste reaction remains incompletely understood. Through a phosphoproteomic approach, we found the key proteins that trigger taste mechanisms based on the phosphorylation cascades. Thereinto, ryanodine receptor isoform 1 (RYR1) was further verified by sensor and behaviors assay. A model proposing RYR1-mediated sweet/umami signaling: RYR1 channel which mediates Ca2+ release from the endoplasmic reticulum is closed by its dephosphorylation in the bud tissue after umami/sweet treatment. And the alteration of Ca2+ content in the cytosol induces a transient membrane depolarization and generates cell current for taste signaling transduction. We demonstrate that RYR1 is a new channel in regulation of sweet/umami signaling transduction and also propose a metabolic clock notion based on sweet/umami sensing. Our study provides a rich fundamental for a system-level understanding of taste perception mechanism.

Cyanobacterial Phytochromes in Optogenetics

Optogenetics initially used plant photoreceptors to monitor neural circuits, later it has expanded to include engineered plant photoreceptors. Recently photoreceptors from bacteria, algae and cyanobacteria have been used as an optogenetic tool. Bilin-based photoreceptors are common light-sensitive photoswitches in plants, algae, bacteria and cyanobacteria. Here we discuss the photoreceptors from cyanobacteria. Several new photoreceptors have been explored in cyanobacteria which are now proposed as cyanobacteriochrome. The domains in the cyanobacteriochrome, light-induced signaling transduction, photoconversion, are the most attractive features for the optogenetic system. The wider spectral feature of cyanobacteriochrome from UV to visible radiation makes it a light potential sensitive optogenetic tool. Besides, cyanobacterial phytochrome responses to yellow, orange and blue light have more application in optogenetics. This chapter summarizes the photoconversion, phototaxis, cell aggregation, cell signaling mediated by cyanobacteriochrome and cyanophytochrome. As there is a wide range of cyanobacteriochrome and its combination delivers a varied light-sensitive response. Besides coordination among cyanobacteriochromes in cell signaling reduces the engineering of photoreceptors for the optogenetic system.