From Hofmeister to hydrotrope: Effect of anion hydrocarbon chain length on a polymer brush
Robertson, Hayden
;
Willott, Joshua D.
;
Gregory, Kasimir P.
, et al.
J. Colloid Interf. Sci.,2023,634,983-994.
DOI:
10.1016/j.jcis.2022.12.114
PubMed ID:
36571860
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Abstract: Hypothesis
Specific ion effects govern myriad biological phenomena, including protein–ligand interactions and enzyme activity. Despite recent advances, detailed understanding of the role of ion hydrophobicity in specific ion effects, and the intersection with hydrotropic effects, remains elusive. Short chain fatty acid sodium salts are simple amphiphiles which play an integral role in our gastrointestinal health. We hypothesise that increasing a fatty acid’s hydrophobicity will manifest stronger salting-out behaviour.
Experiments
Here we study the effect of these amphiphiles on an exemplar thermoresponsive polymer brush system, conserving the carboxylate anion identity while varying anion hydrophobicity via the carbon chain length. Ellipsometry and quartz crystal microbalance with dissipation monitoring were used to characterise the thermoresponse and viscoelasticity of the brush, respectively, whilst neutron reflectometry was used to reveal the internal structure of the brush. Diffusion-ordered nuclear magnetic resonance spectroscopy and computational investigations provide insight into polymer-ion interactions.
Findings
Surface sensitive techniques unveiled a non-monotonic trend in salting-out ability with increasing anion hydrophobicity, revealing the bundle-like morphology of the ion-collapsed system. An intersection between ion-specific and hydrotropic effects was observed both experimentally and computationally; trending from good anti-hydrotrope towards hydrotropic behaviour with increasing anion hydrophobicity, accompanying a change in hydrophobic hydration.
Keywords:
Hofmeister ;
Hydrophobic effect ;
Hydrotrope ;
Polymer brush ;
Short-chain fatty acids ;
Specific ion effects ;
Surface chemistry ;
Thin films
Purchased from AmBeed:
6106-41-8
Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice
Suresh C Bokoliya
;
Jordan Russel
;
Yair Dorsett
, et al.
Research Square,2023.
DOI:
10.21203/rs.3.rs-3496323/v1
PubMed ID:
38886761
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Abstract: Background:
Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. Development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied.
Results:
Here, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acidshort-chain-fatty-acid with similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome.
Conclusion:
Our findings suggest that the sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms.
Keywords:
Alcohol drinking ;
SCFA ;
Sodium valerate ;
GABA ;
Microbiome
Purchased from AmBeed:
6106-41-8
Impact of gut metabolites and antibiotics on immune responses
Krimitza, Elisavet
;
PERELMAN SCHOOL OF MEDICINE,2022.
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Abstract: Gut microbiota –the assembly of commensal intestinal microorganisms - impacts the host immune system in several ways. Antibiotics -widely used therapeutic agents- are able to modulate the survival and the growth of gut bacteria, as well as the metabolites they produce. Some gut bacteria are already known to affect the T cell development and differentiation. This research thesis investigates the impact that certain antibiotics and metabolites (short chain fatty acids) could have on antigen presentation and T cell activation. Through series of assays evaluating the antigen presentation to CD8+ T cells, this thesis has shown that different metabolites have distinct effects, some are able to boost and others to inhibit the immune responses. We suggest that different metabolites may act through distinct signaling and cytokine transduction pathways. Factors like the concentrations, the timing and the duration of exposure of the APCs to those treatments, together with the type of the metabolite, might hold a role in the activation of different pathways as well. Among the metabolites we tested, propionate was shown to have inhibitory effects on antigen presentation, and the mechanism behind this is probably related to the antigen processing, through upregulation of the IFNα gene. Butyrate might be regulating the expression of the MHC II gene. Antibiotics were found to have no direct impact on T cell activation in vitro or in vivo. Even though the complexity of the gut microbiota impact on the immune system still needs further studies, we overall suggest that fine regulation of the gut metabolites can largely affect the clinical outcomes of multiple therapies.
Keywords:
gut microbiome ;
immune system ;
metabolites ;
antigen presentation ;
T cell activation
Purchased from AmBeed:
6106-41-8
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