ABSTRACT
This study focused on the effects of freeze drying (FD) and sprays drying (SD) on the structure and emulsifying properties of yam soluble protein (YSP). The results showed that the surface hydrophobicity (Ho) value, free sulfhydryl group (SH) content, turns content, denaturation temperature and enthalpy value of spray-dried YSP (SD-YSP) were higher than freeze-dried YSP (FD-YSP), but the apparent hydrodynamic diameter (Dh) value of SD-YSP was smaller. The smaller Dh, higher Ho and free SH led to higher percentage of adsorbed proteins and stronger binding between protein and oil droplet in emulsions. Thus, the emulsifying properties of SD-YSP were better, and the SD-YSP-stabilized emulsion had better dynamical rheological properties. Molecular dynamics (MD) simulations suggested that some intramolecular disulfide bonds and hydrogen bonds of dioscorin were broken, and some helices transformed into turns during the SD process. These structural changes resulted in better thermal stability and emulsification properties of SD-YSP.
Subject(s)
Dioscorea , Molecular Dynamics Simulation , Spray Drying , Freeze Drying/methods , Emulsions/chemistryABSTRACT
α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83+/- mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.
Subject(s)
Ganglia, Autonomic/physiopathology , Pure Autonomic Failure/pathology , Synucleinopathies/pathology , alpha-Synuclein/metabolism , Animals , Behavior Observation Techniques , Disease Models, Animal , Ganglia, Autonomic/pathology , Humans , Male , Mice , Mice, Transgenic , Mutation , Protein Aggregates , Pure Autonomic Failure/genetics , Pure Autonomic Failure/physiopathology , Synucleinopathies/genetics , Synucleinopathies/physiopathology , alpha-Synuclein/administration & dosage , alpha-Synuclein/geneticsSubject(s)
Astrocytes/metabolism , Bone Neoplasms/metabolism , Bone Neoplasms/physiopathology , Cancer Pain/drug therapy , Cancer Pain/metabolism , Palmitates/therapeutic use , Animals , Caspase 3/metabolism , Cell Line , Cell Line, Tumor , Female , Membrane Potential, Mitochondrial/physiology , Mitochondrial Dynamics/physiology , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , bcl-2-Associated X Protein/metabolismABSTRACT
Bone cancer pain (BCP) is the pain induced by primary bone cancer or tumor metastasis. Increasing evidence and our previous studies have shown that mammalian silent information regulator 2â¯homolog (SIRT1) is involved in periphery sensitization and central sensitization of BCP, and the underlying mechanism of SIRT1 in bone cancer pain may provide clues for pain treatment. Dynamin-related protein 1 (Drp1) is an essential regulator for mitochondrial fission. In this research, BCP model rats were established by injecting MRMT-1 rat mammary gland carcinoma cells into the left tibia of female Sprague-Dawley rats and validated by tibia radiographs, histological examination and mechanical pain test. As a result BCP rats exhibited bone destruction and sensitivity mechanical pain. BCP increased inflammatory cells infiltration and apoptosis, reduced SIRT1 protein expression and phosphorylation, and elevated Drp1 expression in spinal cord. An agonist of SIRT1 named SRT1720 intrathecal treatment in BCP rats increased SIRT1 phosphorylation, reduced the up-regulated Drp1 expression, and reversed pain behavior. SRT1720 also regulated Bcl-2/BAX and cleaved caspase-3 expressions, and inhibited mitochondrial apoptosis in spinal cord of BCP rats. For in vitro research, SRT1720 treatment decreased Drp1 expression in a dose-dependent manner, blocked CCCP-induced mitochondrial membrane potential change, consequently reduced apoptosis and promoted proliferation. These data suggest that SIRT1 activation by SRT1720 attenuated bone cancer pain via preventing Drp1-mediated mitochondrial fission. Our results provide new targets for therapeutics of bone cancer pain.