Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments.

Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of NAFLD is widely recognised, the precise triggers for disease progression are still to be fully elucidated. Furthermore, the propagation to cirrhosis is poorly understood. Whilst some progress in terms of treatment options have been explored, an incomplete understanding of the hepatic cellular and molecular alterations limits their clinical utility. We have therefore reviewed some of the key pathways responsible for the pathogenesis of NAFLD such as innate and adaptative immunity, lipotoxicity and fibrogenesis, and highlighted current trials and treatment options for NAFLD patients. [Abstract copyright: ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Alcoholic liver disease: Current insights into cellular mechanisms.

Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of ALD is widely recognized, the precise triggers for disease progression are still to be fully elucidated. Oxidative stress, mitochondrial dysfunction, gut dysbiosis and altered immune system response plays an important role in disease pathogenesis, triggering the activation of inflammatory pathways and apoptosis. Despite many recent clinical studies treatment options for ALD are limited, especially at the alcoholic hepatitis stage. We have therefore reviewed some of the key pathways involved in the pathogenesis of ALD and highlighted current trials for treating patients. [Abstract copyright: ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Dry Powder Formulation of Azithromycin for COVID-19 Therapeutics

Aim: The aim of this study is to develop dry powder formulations of azithromycin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocomposite microparticles for pulmonary delivery to improve the low bioavailability of azithromycin. Methods: Double emulsion method was used to produce nanoparticles, which were then spray dried to form nanocomposite microparticles. Encapsulation efficiency and drug loading were analysed, and formulations were characterised by particle size, zeta potential, morphology, crystallinity and in-vitro aerosol dispersion performance. Results: The addition of chitosan changed the neutrally-charged azithromycin only formulation to positively-charged nanoparticles. However, the addition of chitosan also increased the particle size of the formulations. It was observed in the NGI® data that there is an improvement in dispersibility of the chitosan-related formulations. Conclusion: It was demonstrated in this study that all dry powder formulations were able to deliver azithromycin to the deep lung regions, which suggests the potential of using azithromycin via pulmonary drug delivery as an effective method to treat COVID-19

Comparative Assessment of the Acute Effects of Whey, Rice and Potato Protein Isolate Intake on Markers of Glycaemic Regulation and Appetite in Healthy Males Using a Randomised Study Design

Global protein consumption has been increasing for decades due to changes in demographics and consumer shifts towards higher protein intake to gain health benefits in performance nutrition and appetite regulation. Plant-derived proteins may provide a more environmentally sustainable alternative to animal-derived proteins. This study, therefore, aimed to investigate, for the first time, the acute effects on glycaemic indices, gut hormones, and subjective appetite ratings of two high-quality, plant-derived protein isolates (potato and rice), in comparison to a whey protein isolate in a single-blind, triple-crossover design study with nine male participants (30.8 ± 9.3 yrs). Following a 12 h overnight fast, participants consumed an equal volume of the three isocaloric protein shakes on different days, with at least a one-week washout period. Glycaemic indices and gut hormones were measured at baseline, then at 30, 60, 120, 180 min at each visit. Subjective palatability and appetite ratings were measured using visual analogue scales (VAS) over the 3 h, at each visit. This data showed significant differences in insulin secretion with an increase in whey (+141.8 ± 35.1 pmol/L; = 0.011) and rice (-64.4 ± 20.9 pmol/L; = 0.046) at 30 min compared to potato protein. A significantly larger total incremental area under the curve (iAUC) was observed with whey versus potato and rice with < 0.001 and = 0.010, respectively. There was no significant difference observed in average appetite perception between the different proteins. In conclusion, this study suggests that both plant-derived proteins had a lower insulinaemic response and improved glucose maintenance compared to whey protein

Mouth Rinsing With a Pink Non-caloric, Artificially-Sweetened Solution Improves Self-Paced Running Performance and Feelings of Pleasure in Habitually Active Individuals

Purpose: The purpose of this study was to investigate whether mouth rinsing with a pink non-caloric, artificially sweetened solution can improve self-selected running speed and distance covered during a 30 min running protocol. Methods: Ten healthy and habitually active individuals (six males, four females) completed two experimental trials in a randomised, single-blind, crossover design. Each experimental trial consisted of a 30 min treadmill run at a self-selected speed equivalent to 15 (hard/heavy) on the rating of perceived exertion scale. During exercise, participants mouth rinsed with either a pink or a clear non-caloric, artificially sweetened solution, with performance, perceptual and physiological measures obtained throughout. Results: Self-selected running speed (+0.4 ± 0.5 km·h−1, p = 0.024, g = 0.25) and distance covered (+213 ± 247 m, p = 0.023, g = 0.25) during the 30 min running protocol were both improved by 4.4 ± 5.1% when participants mouth rinsed with the pink solution when compared to the clear solution. Feelings of pleasure were also enhanced during the 30 min treadmill run when participants mouth rinsed with the pink solution, with ratings increased from 3.4 ± 0.7 in the clear condition to 3.8 ± 0.6 in the pink condition (+0.4 ± 0.5, p = 0.046, g = 0.54). Conclusion: Mouth rinsing with a pink non-caloric, artificially sweetened solution improved self-selected running speed, total distance covered, and feelings of pleasure obtained during a 30 min running protocol when compared to an isocaloric and taste-matched clear solution

Dry powder formulation of azithromycin for COVID-19 therapeutics

Aim: The aim of this study is to develop dry powder formulations of azithromycin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocomposite microparticles for pulmonary delivery to improve the low bioavailability of azithromycin. Methods: Double emulsion method was used to produce nanoparticles, which were then spray dried to form nanocomposite microparticles. Encapsulation efficiency and drug loading were analysed, and formulations were characterised by particle size, zeta potential, morphology, crystallinity and in-vitro aerosol dispersion performance. Results: The addition of chitosan changed the neutrally-charged azithromycin only formulation to positively-charged nanoparticles. However, the addition of chitosan also increased the particle size of the formulations. It was observed in the NGI® data that there is an improvement in dispersibility of the chitosan-related formulations. Conclusion: It was demonstrated in this study that all dry powder formulations were able to deliver azithromycin to the deep lung regions, which suggests the potential of using azithromycin via pulmonary drug delivery as an effective method to treat COVID-19

Formulated Palmitoylethanolamide Supplementation Improves Parameters of Cognitive Function and BDNF Levels in Young, Healthy Adults:A Randomised Cross-Over Trial

Background: Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator which is naturally produced in the body and found in certain foods. The aim of this study was to assess the effect of a bioavailable formulated form of PEA (Levagen+®) on serum BDNF levels and parameters of cognitive function in healthy adults. Methods: A randomised double-blinded placebo-controlled cross-over trial was implemented to measure the effects of a 6-week 700 mg/day course of formulated PEA supplementation versus a placebo. Participants (n = 39) completed pre- and post-assessments of a lab-based cognitive test. Serum samples were collected to measure BDNF concentrations using an immunoassay. Results: A significant increase in serum BDNF levels was found following PEA supplementation compared with the placebo (p = 0. 0057, d = 0.62). The cognition test battery demonstrated improved memory with PEA supplementation through better first success (p = 0.142, d = 0.54) and fewer errors (p = 0.0287; d = −0.47) on the Paired Associates Learning test. Conclusion: This was the first study to report a direct beneficial effect of Levagen+® PEA supplementation on memory improvement as well as corresponding increases in circulating neurotrophic marker levels. This suggests that formulated PEA holds promise as an innovative and practical intervention for cognitive health enhancement

Antifungal nanosuspensions with surfactants and silver for the treatment of onychomycosis.

Fungal nail infection (Onychomycosis) often requires prolonged treatment and is associated with a high risk of resistance to treatment. Here in this contribution, we introduce a novel approach to enhance penetration and antifungal activity of the antifungal drug griseofulvin (GF). Solid dispersions were prepared with hydroxypropyl methylcellulose acetate succinate (HPMCAS) and combined with surfactant (either sodium dodecyl sulphate (SDS), dodecyl trimethylammonium bromide (DTAB), or Pluronic F127) using mechanochemical activation. The prepared powders were then suspended with spray-dried silica-coated silver nanoparticles and applied onto infected bovine hooves to assess permeability and antifungal activity. The results showed that the prepared nanosuspensions significantly suppressed fungal activity causing disruption of fungal biofilms. Raman mapping showed enhanced permeation while dynamic vapor sorption (DVS), and particle size measurements showed varied effects depending on the type of surfactant and milling conditions. The prepared nanosuspensions displayed enhanced solubility of the poorly soluble drug reaching approximately 1.2 mg/mL. The results showed that the dispersions that contained DTAB displayed maximum efficacy while the inclusion of colloidal silver did not seem to significantly improve the antifungal activity compared to other formulations. [Abstract copyright: Copyright © 2022. Published by Elsevier B.V.

Incentivised physical activity intervention promoting daily steps among university employees in the workplace through a team-based competition

Introduction: The benefits of walking on health and well-being is well established and regarded as the most accessible form of physical activity (PA) that most individuals can incorporate into their lives. Despite the benefits, the impact of a competitive walking intervention combined with a prize incentive in the workplace is yet to be established. The aim of this intervention was to promote PA among university employees through teams-based competition with a prize incentive targeted towards the recommended 10,000 steps per day. Methods: A total of 49 employees participated and formed eight departmental teams ranging from Senior Admin management, Educational &amp; Social work, Nursing &amp; Midwifery, Sport &amp; Exercise, Health Sciences, Admin Assistant, Library, and IT to compete in a walking intervention. Each team was handed an ActiGraph wGT3X-BT from Monday to Friday to record their walking steps. Steps. Post intervention participants completed an open-ended survey to provide their views about the intervention. Results: The ActiGraph findings determined that steps increased by 4,799 per day from daily baseline of 5,959 to 10,758 throughout this intervention. The themes from qualitative data showed that the prize incentive and competitive nature of this intervention has motivated staff to walk more, changed their behaviour, enjoyed the team-based competition, and improved perceived productivity in the workplace. Discussion and conclusion: This intervention increased employees’ daily steps by 4,799 and met the 10,000 steps guideline. The ‘Health Sciences’ team recorded the highest steps 531,342 followed by the ‘Education and Social Work’ accumulating 498,045 steps throughout this intervention. This intervention with prize incentive demonstrated a positive impact on employees personal and work-based outcomes as well as contributed to the workplace PA, health, and wellbeing literature, and more specifically, to the scarce research focused on university settings

Excessive iron induces oxidative stress promoting cellular perturbations and insulin secretory dysfunction in MIN6 beta cells

Exposure to high levels of glucose and iron are co-related to reactive oxygen species (ROS) generation and dysregulation of insulin synthesis and secretion, although the precise mechanisms are not well clarified. The focus of this study was to examine the consequences of exposure to high iron levels on MIN6 β-cells. MIN6 pseudoislets were exposed to 20 µM (control) or 100 µM (high) iron at predefined glucose levels (5.5 mM and 11 mM) at various time points (3, 24, 48 &amp; 72 h). Total iron content was estimated by a colourimetric ferrozine assay in presence or absence of transferrin-bound iron. Cell viability was assessed by a resazurin dye-based assay, and ROS mediated cellular oxidative stress was assessed by estimating malondialdehyde levels. β-cell iron absorption was de-termined by a ferritin immunoassay. Cellular insulin release and content was measured by an insu-lin immunoassay. Expression of SNAP-25, a key protein in the core SNARE complex that modulates vesicle exocytosis, was measured by immunoblotting. Our results demonstrate that exposure to high iron levels resulted in a 15-fold (48 h) and 4-fold (72 h) increase in cellular iron accumulation. These observations were consistent with data from oxidative stress analysis which demonstrated 2.69-fold higher levels of lipid peroxidation. Furthermore, exposure to supraphysiological (11 mM) levels of glucose and high iron (100 µM) at 72 h exerted the most detrimental effect on the MIN6 β-cell viability. The effect of high iron exposure on total cellular iron content was identical in the pres-ence or absence of transferrin. High iron exposure (100 µM) resulted in a decrease of MIN6 insulin secretion (64% reduction) as well as cellular insulin content (10% reduction). Finally, a significant reduction in MIN6 β-cell SNAP-25 protein expression was evident at 48 h upon exposure to 100 µM iron. Our data suggest that exposure to high iron and glucose concentrations results in cellular ox-idative damage and may initiate insulin secretory dysfunction in pancreatic β-cells by modulation of the exocytotic machinery