Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review

The term “metabolic syndrome” (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting β cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS

On the estimation of viscosities and densities of CO2-loaded MDEA, MDEA + AMP, MDEA + DIPA, MDEA + MEA, and MDEA + DEA aqueous solutions

As noteworthy properties of amine aqueous solutions, the densities and viscosities of aqueous N-Methyldiethanolamine (MDEA) solutions and mixtures of MDEA with 2-Amino-2-methyl-1-propanol (AMP), Diisopropanolamine (DIPA), Monoethanolamine (MEA), and Diethanolamine (DEA) were estimated under CO2 gas loading using Adaptive Neuro-Fuzzy Inference System (ANFIS), Multi-Layer Perceptron Artificial Neural Network (MLPANN), Support Vector Machine (SVM), and Least Square Support Vector Machine (LSSVM). The density and viscosity were estimated as a function of temperature, CO2 loading, pressure, and molecular weight of mixtures. In this regard, the actual data points were collected from the literature. Genetic Algorithm (GA) was employed to determine hyper variables of the LSSVM approach and Levenberg–Marquardt algorithm was employed to optimize bias and weight values of the ANN model. In addition, Particle Swarm Optimization algorithm (PSO) was used to determine membership parameters of the ANFIS approach and related parameters of the SVM were optimized using GA. The developed tools can be of massive value for chemical engineers and chemists to have a quick check of the densities and viscosities of the aforementioned amine solutions. Results obtained from the proposed models are in satisfactory agreement with actual data. According to statistical analyses, while the obtained values of Mean Squared Error (MSE) and R-squared (R2) for estimating densities of amine solutions are 0.000011 and 0.9938, 0.000013 and 0.9937, 0.000009 and 0.9953, 0.000001 and 0.9993 for the ANN, ANFIS, SVM, and LSSVM models respectively, these values obtained 0.079 and 0.994, 0.113 and 0.9911, 0.0634 and 0.9971, 0.0079 and 0.9996 for estimating the viscosities of amine-based solutions

A pre-catalytic non-covalent step governs DNA polymerase β fidelity

DNA polymerase beta (pol beta) selects the correct deoxyribonucleoside triphosphate for incorporation into the DNA polymer. Mistakes made by pol beta lead to mutations, some of which occur within specific sequence contexts to generate mutation hotspots. The adenomatous polyposis coli (APC) gene is mutated within specific sequence contexts in colorectal carcinomas but the underlying mechanism is not fully understood. In previous work, we demonstrated that a somatic colon cancer variant of pol beta, K289M, misincorporates deoxynucleotides at significantly increased frequencies over wild-type pol beta within a mutation hotspot that is present several times within the APC gene. Kinetic studies provide evidence that the rate-determining step of pol beta catalysis is phosphodiester bond formation and suggest that substrate selection is governed at this step. Remarkably, we show that, unlike WT, a pre-catalytic step in the K289M pol beta kinetic pathway becomes slower than phosphodiester bond formation with the APC DNA sequence but not with a different DNA substrate. Based on our studies, we propose that precatalytic conformational changes are of critical importance for DNA polymerase fidelity within specific DNA sequence contexts.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Probing DNA Base-Dependent Leaving Group Kinetic Effects on the DNA Polymerase Transition State

We examine the DNA polymerase β (pol β) transition state (TS) from a leaving group pre-steady-state kinetics perspective by measuring the rate of incorporation of dNTPs and corresponding novel β,γ-CXY-dNTP analogues, including individual β,γ-CHF and -CHCl diastereomers with defined stereochemistry at the bridging carbon, during the formation of right (R) and wrong (W) base pairs. Brønsted plots of log <i>k</i>_pol versus p<i>K</i>_a4 of the leaving group bisphosphonic acids are used to interrogate the effects of the base identity, the dNTP analogue leaving group basicity, and the precise configuration of the C-X atom in <i>R</i> and <i>S</i> stereoisomers on the rate-determining step (<i>k</i>_pol). The dNTP analogues provide a range of leaving group basicity and steric properties by virtue of monohalogen, dihalogen, or methyl substitution at the carbon atom bridging the β,γ-bisphosphonate that mimics the natural pyrophosphate leaving group in dNTPs. Brønsted plot relationships with negative slopes are revealed by the data, as was found for the dGTP and dTTP analogues, consistent with a bond-breaking component to the TS energy. However, greater multiplicity was shown in the linear free energy relationship, revealing an unexpected dependence on the nucleotide base for both A and C. Strong base-dependent perturbations that modulate TS relative to ground-state energies are likely to arise from electrostatic effects on catalysis in the pol active site. Deviations from a uniform linear Brønsted plot relationship are discussed in terms of insights gained from structural features of the prechemistry DNA polymerase active site