Higher fasting fibroblast growth factor 21 was associated with a greater decline in postprandial blood pressure.

BACKGROUND: A fall in blood pressure (BP) following a meal is well known and is usually a transient phenomenon, due to appropriate cardiovascular adjustments. Older individuals and those with high BP experience a greater postprandial fall that can manifest as postprandial hypotension (PPH). Fibroblast growth factor 21 (FGF21) is positively associated with BP, and is known to increase after meal ingestion. We explored whether fasting FGF21 or its postprandial change would be associated with meal induced BP change, after accounting for several covariates. METHODS: Eighty-three Western Australian adults were studied. Supine resting BP was recorded and an oral glucose test was administered. Serial measurements of systolic BP (SBP) and diastolic BP (DBP) were then made in duplicate every 30 min up to 120 min. Fasting and 120 min blood samples were analysed for FGF21 and clinical chemistry. Multiple linear regression analyses of the incremental area under curve of postprandial SBP and DBP was conducted on 12 known determinants. RESULTS: The final parsimonious model based on backward regression of postprandial SBP included fasting SBP, gender, fasting insulin and fasting FGF21 (ß = -0.009 (95% confidence interval (CI): 0.017, -0.002, P = 0.015)). For postprandial DBP these included fasting DBP, gender, fasting glucose, fasting insulin and fasting FGF21 (ß = -0.005; 95% CI: 0.010, -0.001, P = 0.021). CONCLUSIONS: A higher fasting FGF21, independent of glucose and insulin, was associated with a greater postprandial decline in SBP and in DBP.

A high-throughput, 28-day, microfluidic model of gingival tissue inflammation and recovery.

Nearly half of American adults suffer from gum disease, including mild inflammation of gingival tissue, known as gingivitis. Currently, advances in therapeutic treatments are hampered by a lack of mechanistic understanding of disease progression in physiologically relevant vascularized tissues. To address this, we present a high-throughput microfluidic organ-on-chip model of human gingival tissue containing keratinocytes, fibroblast and endothelial cells. We show the triculture model exhibits physiological tissue structure, mucosal barrier formation, and protein biomarker expression and secretion over several weeks. Through inflammatory cytokine administration, we demonstrate the induction of inflammation measured by changes in barrier function and cytokine secretion. These states of inflammation are induced at various time points within a stable culture window, providing a robust platform for evaluation of therapeutic agents. These data reveal that the administration of specific small molecule inhibitors mitigates the inflammatory response and enables tissue recovery, providing an opportunity for identification of new therapeutic targets for gum disease with the potential to facilitate relevant preclinical drug efficacy and toxicity testing.

Naringin@Metal-Organic Framework as a Multifunctional Bioplatform.

Naringin, a natural product, can be used as a therapeutic agent due to its low systemic toxicity and negligible adverse effect. However, due to its hydrophobic nature and thereby low solubility, high-dose treatment is required when used for human therapy. Herein, we demonstrate the employment of a metal-organic framework (MOF) as a nontoxic loading carrier to encapsulate naringin, and the afforded nairngin@MOF composite can serve as a multifunctional bioplatform capable of treating Gram-positive bacteria and certain cancers by slowly and progressively releasing the encapsulated naringin as well as improving and modulating immune system functions through synergy between naringin and the MOF.

Corrigendum to "Challenges to assumptions regarding oral shear rate during oral processing and swallowing based on sensory testing with thickened liquids" [Food Hydrocolloids 84C (2018) 173-180].

[This corrects the article PMC6367734.].

Modulation of Tongue Pressure According to Liquid Flow Properties in Healthy Swallowing.

Purpose During swallowing, the tongue generates the primary propulsive forces that transport material through the oral cavity toward the pharynx. Previous literature suggests that higher tongue pressure amplitudes are generated for extremely thick liquids compared with thin liquids. The purpose of this study was to collect detailed information about the modulation of tongue pressure amplitude and timing across the range from thin to moderately thick liquids. Method Tongue pressure patterns were measured in 38 healthy adults (aged under 60 years) during swallowing with 4 levels of progressively thicker liquid consistency (International Dysphagia Diet Standardisation Initiative, Levels 0 = thin, 1 = slightly thick, 2 = mildly thick, and 3 = moderately thick). Stimuli with matching gravity flow (measured using the International Dysphagia Diet Standardisation Initiative Flow Test; Cichero et al., 2017 ; Hanson, 2016 ) were prepared both with/without barium (20% weight per volume concentration) and thickened with starch and xanthan gum thickeners. Results After controlling for variations in sip volume, thicker liquids were found to elicit significantly higher amplitudes of peak tongue pressure and a pattern of higher (i.e., steeper) pressure rise and decay slopes (change in pressure per unit time). Explorations across stimuli with similar flow but prepared with different thickeners and with/without barium revealed very few differences in tongue pressure, with the exception of significantly higher pressure amplitudes and rise slopes for nonbarium, starch-thickened slightly and mildly thick liquids. Conclusions There was no evidence that the addition of barium led to systematic differences in tongue pressure parameters across liquids with closely matched gravity flow. Additionally, no significant differences in tongue pressure parameters were found across thickening agents. Supplemental Material https://doi.org/10.23641/asha.7616537.

Sensory characteristics of liquids thickened with commercial thickeners to levels specified in the International Dysphagia Diet Standardization Initiative (IDDSI) framework.

Sensory characteristics are important for the acceptance of thickened liquids, but those of liquids thickened to the new standards put forth by the International Dysphagia Diet Standardization Initiative (IDDSI) are unknown. This research sought to identify and rate the perception of important sensory properties of liquids thickened to levels specified in the IDDSI framework. Samples were made with water, with and without added barium sulfate, and were thickened with a cornstarch or xanthan gum based thickener. Samples were characterized using projective mapping/ultra-flash profiling to identify important sample attributes, and then with trained descriptive analysis panels to characterize those attributes in non-barium and barium thickened liquids. Three main groups of attributes were observed. Taste and flavor attributes decreased in intensity with increasing thickener. Thickener specific attributes included graininess and chalkiness for the cornstarch thickened samples, and slipperiness for the xanthan gum samples. Within the same type of thickener, ratings of thickness-related attributes (perceived viscosity, adhesiveness, manipulation, and swallowing) at different IDDSI levels were significantly different from each other. However, in non-barium samples, cornstarch samples were perceived as thicker than xanthan gum samples even though they had similar apparent viscosities at 50 s-1. On the other hand, the two thickeners had similar perceived thickness in the barium samples even though the apparent viscosities of cornstarch samples were higher than those of the xanthan gum samples. In conclusion, IDDSI levels can be distinguished based on sensory properties, but these properties may be affected by the type of thickener and medium being thickened.

Challenges to assumptions regarding oral shear rate during oral processing and swallowing based on sensory testing with thickened liquids.

For people with dysphagia, or difficulty swallowing, thickened liquids are used to slow bolus flow to make them easier to control. For these liquids, the oral shear rate of 50 s-1 has been adopted as the standard at which viscosity measurements are taken. However, there is evidence to suggest that other shear rates may be more appropriate to model the processes in the mouth and throat. This research compared the sensory and rheological properties of xanthan gum, guar gum, and carboxymethyl cellulose thickened liquids that had been matched for apparent viscosity at 50 s-1 to assess the validity of the current shear rate standard. Properties of gums were observed at various viscosity levels based on the International Dysphagia Diet Standardisation Initiative (IDDSI) framework. Textural sensory characteristics of samples were quantified using magnitude estimation scaling and a trained descriptive panel, while rheological measurements were taken at shear rates of 1 to 1000 s-1. Perceived slipperiness of the gums was found to be driven by thickness level at low viscosity levels, but affected by the shear thinning behavior of the gums at higher viscosity levels. Although the liquids had been matched for apparent viscosity at 50 s-1, panelists could distinguish both the perceived viscosities of the gums and their ease of swallowing, suggesting that 50 s-1 is neither appropriate to model the oral nor pharyngeal shear rates. A single oral shear rate could not be predicted from the data, and it is proposed that panelists evaluated oral viscosity using different methods at different viscosity levels. Based on the sensory data, the pharyngeal shear rate during swallowing appears to lie above 50 s-1.

Development and Characterization of In Vitro Human Oral Mucosal Equivalents Derived from Immortalized Oral Keratinocytes.

Tissue-engineered oral mucosal equivalents (OME) are being increasingly used to measure toxicity, drug delivery, and to model oral diseases. Current OME mainly comprise normal oral keratinocytes (NOK) cultured on top of a normal oral fibroblasts-containing matrix. However, the commercial supply of NOK is limited, restricting widespread use of these mucosal models. In addition, NOK suffer from poor longevity and donor-to-donor variability. Therefore, we constructed, characterized, and tested the functionality of OME based on commercial TERT2-immortalized oral keratinocytes (FNB6) to produce a more readily available alternative to NOK-based OME. FNB6 OME cultured at an air-to-liquid interface for 14 days exhibited expression of differentiation markers cytokeratin 13 in the suprabasal layers and cytokeratin 14 in basal layer of the epithelium. Proliferating cells were restricted to the basal epithelium, and there was immuno-positive expression of E-cadherin confirming the presence of established cell-to-cell contacts. The histology and expression of these structural markers paralleled those observed in the normal oral mucosa and NOK-based models. On stimulation with TNFα and IL-1, FNB6 OME displayed a similar global gene expression profile to NOK-based OME, with increased expression of many common pro-inflammatory molecules such as chemokines (CXCL8), cytokines (IL-6), and adhesion molecules (ICAM-1) when analyzed by gene array and quantitative PCR. Similarly, pathway analysis showed that both FNB6 and NOK models initiated similar intracellular signaling on stimulation. Gene expression in FNB6 OME was more consistent than NOK-based OME that suffered from donor variation in response to stimuli. Mucosal equivalents based on immortalized FNB6 cells are accessible, reproducible and will provide an alternative animal experimental system for studying mucosal drug delivery systems, host-pathogen interactions, and drug-induced toxicity.

The genetic design of signaling cascades to record receptor activation.

We have developed an experimental strategy to monitor protein interactions in a cell with a high degree of selectivity and sensitivity. A transcription factor is tethered to a membrane-bound receptor with a linker that contains a cleavage site for a specific protease. Activation of the receptor recruits a signaling protein fused to the protease that then cleaves and releases the transcription factor to activate reporter genes in the nucleus. This strategy converts a transient interaction into a stable and amplifiable reporter gene signal to record the activation of a receptor without interference from endogenous signaling pathways. We have developed this assay for three classes of receptors: G protein-coupled receptors, receptor tyrosine kinases, and steroid hormone receptors. Finally, we use the assay to identify a ligand for the orphan receptor GPR1, suggesting a role for this receptor in the regulation of inflammation.