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First-order compartment models are common tools for modelling many biological processes, including pharmacokinetics. Given the compartments and the transfer rates, solutions for the time-dependent quantity (or concentration) curves can normally be described by a sum of exponentials. This paper investigates cases that go beyond simple sums of exponentials. With specific relations between the transfer rate constants, two exponential rate constants can be equal, in which case the normal solution cannot be used. The conditions for this to occur are discussed, and advice is provided on how to circumvent these cases. An example of an analytic solution is given for the rare case where an exact equality is the expected result. Furthermore, for models with at least three compartments, cases exist where the solution to a real-valued model involves complex-valued exponential rate constants. This leads to solutions with an oscillatory element in the solution for the tracer concentration, i.e., there are cases where the solution is not a simple sum of (real-valued) exponentials but also includes sine and cosine functions. Detailed solutions for three-compartment cases are given. As a tentative conclusion of the analysis, oscillatory solutions appear to be tied to cases with a cyclic element in the model itself. [ABSTRACT FROM AUTHOR]

Rutin is a flavonoid present in numerous fruits and vegetables and therefore widely consumed by humans. It is also a popular dietary supplement of 250–500 mg/day. There is considerable consumer interest in rutin due to numerous reports in the biomedical literature of its multi-system chemo-preventive properties. The present paper provides the first assessment of rutin-induced hormetic concentration/dose responses, their quantitative features and mechanistic basis, along with their biological, biomedical, clinical, and public health implications. The findings indicate that rutin-induced hormetic dose responses are widespread, being reported in numerous biological models and cell types for a wide range of endpoints. Of critical importance is that the optimal hormetic findings shown in in vitro systems are currently not achievable for human populations due to low gastrointestinal tract bioavailability. These findings have the potential to strengthen future experimental studies with rutin, particularly concerning study design parameters. [Display omitted] • Rutin is a flavonoid present in fruits and vegetables consumed by humans. • Rutin displays multi-system chemo-preventive properties. • First assessment of rutin-induced hormetic dose responses and its implications. • Several biological models and cells show rutin-induced hormetic dose responses. • Findings have the potential to strengthen future experimental studies with rutin. [ABSTRACT FROM AUTHOR]

The learning of QSAR/QSPR models is crucial for predicting the physicochemical properties/biological activities of compounds. For compounds with the same/similar structure, there is a high probability that the molecular descriptors describing the molecular structure undergo degeneracy such that it is impossible to distinguish between these compounds, which in turn leads to modeling failure. In this paper, we construct a two-layer graph structure to design new feature descriptors with high discriminability, and propose a graph signal processing (GSP)-based method for nonlinear QSAR/QSPR model learning for compounds. Considering the molecular descriptors computed based on the molecular graph as a high-dimensional signal, we construct on top of the molecular graph a higher-level graph structure – a compound graph – to describe the similarity between different compounds. We use local complex network metrics to quantify the local topological information on each vertex (compound) in the compound graph, which can naturally be used as new discriminative feature descriptors, based on which we learn two types of nonlinear QSAR/QSPR models. Three datasets with the same/similar molecular graphs are used to learn to model their biological activity, entropy and octanol–water partition coefficient, respectively, and the experimental results well validate the effectiveness of the proposed method. • A GSP-based method for nonlinear QSAR/QSPR model learning of compounds. • Two-layer graph structure to design new feature descriptors with high discriminability. • Three different polynomial/SVR models for three datasets with compounds having the same/similar structure. [ABSTRACT FROM AUTHOR]

This paper represents the first integrative assessment and documentation of taurine-induced hormetic effects in the biological and biomedical areas, their dose response features, mechanistic frameworks, and possible public health, therapeutic and commercial applications. Taurine-induced hormetic effects are documented in a wide range of experimental models, cell types and for numerous biological endpoints, with most of these experimental findings being reported within the past five years. It is suggested that the concept of hormesis may have a transformative effect on taurine research and its public health and therapeutic applications. • Hormesis is a biphasic dose response relationship. • Taurine commonly induces hormetic dose responses. • Numerous tissues show taurine-induced hormesis. • Taurine acts via activation of Nrf2 to induce hormetic effects. [ABSTRACT FROM AUTHOR]

Quercetin is a polyphenol present in numerous fruits and vegetables and therefore widely consumed by humans with average daily dietary intakes of 10–20 mg/day. It is also a popular dietary supplement of 250-1000 mg/day. However, despite the widespread consumer interest in quercetin, due to its possible chemopreventive properties, the extensively studied quercetin presents a highly diverse and complex array of biological effects. Consequently, the present paper provides the first assessment of quercetin-induced hormetic concentration/dose responses, their quantitative features and mechanistic foundations, and their biological, biomedical, clinical, and public health implications. The findings indicate that quercetin-induced hormetic dose responses are widespread, being independent of biological model, cell type, and endpoint. These findings have the potential to enlighten future experimental studies with quercetin especially with respect to study design parameters and may also affect the appraisal of possible public health benefits and risks associated with highly diverse consumer consumption practices. • Quercetin commonly induces hormetic responses. • Hormetic responses induced by quercetin occur in numerous cell types. • Hormetic mechanisms have been reported in numerous studies. • Public health applications are provided. [ABSTRACT FROM AUTHOR]