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In a final experiment, we aimed to circumvent reactance by providing disgusting information under the guise of trivia, thereby avoiding the perception that the disgusting information was meant to manipulate. Via this route, disgust becomes a potent tool to influence consumers' intentions to consume meat. Ethical concerns are discussed.A quantitative understanding of the dose dependence of topical delivery is important to cosmetic and dermatological product development and to risk assessment for hazardous chemicals contacting the skin. Despite considerable research, predictive capability in this area remains limited. To this end we conducted an experimental skin absorption study of two closely related skin care agents, niacinamide (nicotinamide, NA) and methyl nicotinate (MN), and analyzed the results quantitatively using a transient diffusion model described separately (Yu et al. submitted for publication). Radiolabeled test compounds were solvent-deposited onto ex vivo human skin mounted in Franz diffusion cells over a dose range exceeding 4.5 orders of magnitude, and permeation was measured over a 1-4 day period. At low doses, the permeation rate of NA was approximately 60-fold lower than that of its lower melting, more lipophilic analog, MN; at high doses an even greater difference was observed. The difference can be qualitatively explained based on higher lipid solubility and lower crystallinity of MN relative to NA. Dissolution-limited mass transfer through a lipid layer at the SC surface is suggested. Relevance of the results to practical skin care formulations was confirmed by a parallel study of NA in an o/w emulsion.Sterilizing filtration is a common unit operation for the manufacture of parenteral drug products. However, filter performance can be impacted by properties of both the membrane material and the solution being filtered, requiring extensive multi-factor studies to optimize the filtration process for a given drug product. Here, we report the use of a modified bundle of capillaries approximation to predict filter performance. The model is directly applicable for both Newtonian and non-Newtonian solutions and does not require assumptions of steady state. Using a hydrophilic polyvinylidene difluoride (PVDF) filter as a test case, we show that the model fitting parameters align with expected values and both flux and shear are well predicted. Moreover, two case studies are presented to demonstrate the model's utility for filtration process optimization 1) protein adsorption of an antibody formulation and 2) filter fouling of a 1% (w/v) carboxymethylcellulose (CMC) solution. In both cases, the model was able to accurately identify optimal filtration parameters to reduce the amount of adsorption or improve the filter capacity, respectively. This methodology can be easily extended to alternate filter types and provides an additional predictive tool to speed process development and minimize trial and error during filtration process design.In-use stability and compatibility studies are often used in biotherapeutic development to assess stability and compatibility of biologic drugs with diluents and/or administration components at relevant conditions for the target route of administration (commonly intravenous, subcutaneous or intramuscular), to assure that patient safety and product efficacy are maintained during clinical use. To gain an understanding of current industry approaches for in-use stability and compatibility studies, the Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, conducted an inter-company collaboration exercise, which included five bench-marking surveys around in-use stability and compatibility studies of biologic drugs. The results of this industry collaboration provide insights into the practicalities of these studies and how they are being used to support administration of biologics from early clinical programs to marketed products. The surveys queried topics including regulatory strategies and feedback; clinical in-use formulation, patient and site considerations; clinical blinding, masking and placebo approaches; study setup, execution and reporting; and clinical in-use stability and compatibility testing to provide a comprehensive picture of the range of common industry practices. This paper discusses the survey results and presents various approaches which can be used to guide the strategy and design of an in-use stability and compatibility program based on clinical and biomolecule needs.Electrospinning is an advantageous method with a wide usage area, which enables the production of materials consisting of nano-thickness fibers. In this study, caffeic acid phenethyl ester (CAPE) molecule was loaded onto the poly(lactic-co-glycolic acid) (PLGA) nanofibers and obtained nanofibers were physicochemically and biologically investigated for the first time in the literature. The existence of CAPE molecules, loaded on PLGA membranes by dropping and spraying methods, was evaluated by a comparative investigation of Fourier-transform infrared (FTIR) spectra and X-Ray diffraction (XRD) patterns. Fiber morphology of the membranes was investigated by scanning electron microscope (SEM). CAPE release and swelling behaviors of the membranes were studied in vitro. The radical scavenging activity of CAPE-loaded wound dressing materials was determined by using an antioxidant assay. The antimicrobial properties of PLGA and CAPE-loaded PLGA membranes were evaluated against S. https://www.selleckchem.com/products/PD-0332991.html aureus, P. aeruginosa and C. albicans strains by the time-kill method. The biocompatibility study of the obtained CAPE-loaded fibers conducted on human fibroblast cell line and wound healing promoting effect of the fibers was investigated in vitro scratch assay. The results show that CAPE-loaded PLGA membranes are highly antimicrobial against all strains used in the experiment. Additionally, the results show that they are biocompatible and have wound healing properties on human fibroblasts.The occurrence of visible particles over the shelf-life of biopharmaceuticals is considered a potential safety risk for parenteral administration. In many cases, particle formation resulted from the accumulation of fatty acids released by the enzymatic hydrolysis of the polysorbate surfactant by co-purified host cell proteins. However, particle formation can occur before the accumulated fatty acids exceed their expected solubility limit. This early onset of particle formation is driven by nucleation phenomena e.g. the presence of metal cations that promote the formation and growth of fatty acid particles. To further characterize and understand this phenomenon, we assessed the potential of different metal cations to induce fatty acid particle formation using a dynamic light scattering assay. We demonstrated that the presence of trace amounts of multivalent cations, in particular trivalent cations such as aluminum and iron, may act as nucleation seed in the process of particle formation. Finally, we developed a mitigation strategy for metal-induced fatty acid particles that deploys a chelator to reduce the risk of particle formation in biopharmaceutical formulations.The liver has an essential role in responding to metabolic demands under stress conditions. The organ stores, releases, and recycles metabolism-related substrates. However, it is not clear how the Kallikrein-Kinin System modulates metabolic flexibility shift between energetic sources.

To analyze the hepatic metabolism in kinin B1 receptor deficient mice (B1KO mice) under fasting conditions.

WT and B1KO male mice were allocated in a calorimetric cage for 7 days and 48 h before the euthanasia, half of the animals of both groups were under fasting conditions. Biochemical parameters, ketone bodies (KB), and gene expression involving the liver energetic metabolism genes were evaluated.

Kinin B1 receptor (B1R) modulates the metabolic shift under fasting conditions, reducing the VO

expenditure. A preference for carbohydrates as an energetic source is suggested, as the B1KO group did not display an increase in KB in the serum. Moreover, the B1KO animals displayed higher serum triglycerides concentration compared to WT fasting mice. Interestingly, the lack of B1R induces the increase expression of enzymes from the glycolysis and lipolysis pathways under the fed. However, under fasting, the enzymatic expression of gluconeogenesis, glyceroneogenesis, and ketogenesis of these pathways does not occur, suggesting an absence of the shift metabolism responsivity, and this condition is modulated by PDK4 under FOXO1 control.

B1R has an important role in the hepatic glucose metabolism, which in turn influences the energetic metabolism, and in long-term outcomes, such as in the decrease in hepatic glycogen stores and in the enhancement of hepatic metabolism.

B1R has an important role in the hepatic glucose metabolism, which in turn influences the energetic metabolism, and in long-term outcomes, such as in the decrease in hepatic glycogen stores and in the enhancement of hepatic metabolism.

Huntington's disease (HD) is caused by a mutant huntingtin protein that misfolds, yields toxic N-terminal fragments, aggregates, and disrupts proteostasis. The Hsp70 chaperone is a potential therapeutic target as it prevents proteotoxicity by favouring protein folding, disaggregation, or degradation. We tested the hypothesis that allosteric Hsp70 activation with a pharmacological mimetic of the Hsp70 co-chaperone Hip, YM-1, could modulate huntingtin proteostasis.

We used HD cell models expressing either N-terminal or full-length huntingtin. Using single-cell analysis we studied huntingtin aggregation in different cellular compartments by fluorescence microscopy. Protein interaction was evaluated by immunoprecipitation, while protein levels were quantified by immunofluorescence and western-blot.

N-terminal huntingtin interacted with Hsp70 and increased its levels. Treatment with YM-1 reduced N-terminal huntingtin clustering and nuclear aggregation. Full-length mutant huntingtin also interacted with Hsp70ed therapies with Hsp70 elevating strategies could harness the full potential of allosteric Hsp70 activators for HD.Brain aging is a complex process that affects everything from the subcellular to the organ level, begins early in life, and accelerates with age. Morphologically, brain aging is primarily characterized by brain volume loss, cortical thinning, white matter degradation, loss of gyrification, and ventricular enlargement. Pathophysiologically, brain aging is associated with neuron cell shrinking, dendritic degeneration, demyelination, small vessel disease, metabolic slowing, microglial activation, and the formation of white matter lesions. In recent years, the mechanics community has demonstrated increasing interest in modeling the brain's (bio)mechanical behavior and uses constitutive modeling to predict shape changes of anatomically accurate finite element brain models in health and disease. Here, we pursue two objectives. First, we review existing imaging-based data on white and gray matter atrophy rates and organ-level aging patterns. This data is required to calibrate and validate constitutive brain models. Second, we review the most critical cell- and tissue-level aging mechanisms that drive white and gray matter changes.