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Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters-dopamine, serotonin and noradrenaline-and their metabolites were measured. The analysis of mRNA expression of dopamine (D1 and D2), serotonin (5-HT-1 and 5-HT-2) and noradrenaline (α1 and α2a) receptors was also investigated using real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) in the same brain areas. Linagliptin has the ability to influence the dopaminergic system. In the striatum, the elevation of dopamine and its metabolites was observed after repeated administration of that linagliptin, and in the hippocampus, a reduction in dopamine metabolism was demonstrated. Acute linagliptin exposure increases the serotonin level in both areas, while after chronic linagliptin administration a tendency for the mRNA expression of serotoninergic receptors (5-HT1A and 5-HT2A) to increase was observed. A single instance of exposure to linagliptin significantly modified the noradrenaline level in the striatum and intensified noradrenaline turnover in the hippocampus. The recognition of the interactions in the brain between DPP-4 inhibitors and neurotransmitters and/or receptors is a crucial step for finding novel discoveries in the pharmacology of DPP-4 inhibitors and raises hope for further applications of DPP-4 inhibitors in clinical practices.

The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain-gut-microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB‑1) bacteria alters brain metabolites' levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.

(1) Background: Recent data indicate that receptors for GLP-1 peptide are involved in the activity of the mesolimbic system. Thus, the purpose of the present study was to examine the effect of the selective dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on morphine dependence in mice. (2) Methods: Morphine dependence in mice was obtained by administration of increasing doses of morphine for eight consecutive days, twice a day. On the 9th day of the experiment, the naloxone-induced (2 mg/kg, ip) morphine withdrawal signs (jumping) were assessed. Moreover, behavioral effects of short-term (60 h after morphine discontinuation) and long-term (14 days after morphine discontinuation) morphine withdrawal were observed. In terms of behavioral effects, the depressive effect in the forced swim test and anxiety in the elevated plus maze test were investigated. Locomotor activity of mice was also studied. (3) Results: The administration of linagliptin (10 and 20 mg/kg, ip) for 8 consecutive days before morphine injections significantly diminished the number of naloxone-induced morphine withdrawal signs (jumping) in mice. In addition, the cessation of morphine administration induced depressive behavior in mice which were observed during short- and long-term morphine withdrawal. Linagliptin administered during morphine withdrawal significantly reduced the depressive behavior in studied mice. Furthermore, the short-term morphine withdrawal evoked anxiety which also was reduced by linagliptin in mice. (4) Conclusions: The present study reveals that GLP-1 receptors are involved in morphine dependence. What is more, linagliptin might be a valuable drug in attenuating the physical symptoms of morphine dependence. It might be also a useful drug in reducing emotional disturbances which may develop during the morphine withdrawal period.

As a systemic disease, diabetes mellitus (DM) is characterized by the disruption of many glucose metabolic pathways. Therefore, it seems critical to study new therapies to support treatment to develop therapeutic systems that can operate across a broad metabolic spectrum. The current state of knowledge indicates an essential role of the gut microbiota in the development and course of the disease. Cornus mas fruits have demonstrated a rich biological activity profile and potential for application in the treatment of DM. As part of a preliminary analysis, the activity of four cultivars of Cornus mas fruits was analyzed. The cultivar Wydubieckij was selected as having the highest activity in in vitro conditions for further prebiotic system preparation. The study aimed to develop a unique therapeutic system based, first of all, on the mechanism of α-glucosidase inhibition and the antioxidant effect resulting from the activity of the plant extract used, combined with the prebiotic effect of inulin. The obtained system was characterized in vitro in terms of antioxidant activity and enzyme inhibition capacity, and was then tested on diabetic rats. The study was coupled with an analysis of changes in the intestinal microflora. The system of prebiotic stabilized Cornus mas L. lyophilized extract with inulin offers valuable support for the prophylaxis and treatment of DM.

Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B 1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, - 3.2, - 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at - 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B 1  = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure., (© 2021. The Author(s).)

The aim of this paper is to compare the results of kinematic viscosity of lubricating oils measurements at 40 °C, obtained with three different rapid evaluation devices, and the standardized method using an Ubbelohde Capillary viscometer. The following instruments were selected to measure: a mid-FTIR spectrophotometer, a microchannel viscometer, and a Stabinger viscometer. The study material comprised 42 fresh engine oils, all of which are commercially available. The main data analysis tools used in the study were multiple regression, Mahala Nobis distance, post-hoc analysis, and the Wilcoxon signed-rank test with the Bonferroni correction. Consistent outcomes were obtained for the Stabinger viscometer only, whereas the microchannel viscometer and the mid-FTIR spectrophotometer were not as precise as the reference method. It was also found that the results obtained with the use of the mid-FTIR spectrophotometer were burdened with a very large measurement error. Therefore, a very careful approach is suggested when choosing these instruments. The study fills an important gap in empirical research in the context of the reliability of measurement results obtained using various research techniques.

In this paper, we focus on detection of speed changes from audio data, representing recordings of cars passing a microphone placed near the road. The goal of this work is to observe the behavior of drivers near control points, in order to check whether their driving is safe both when approaching the speed camera and after passing it. The audio data were recorded in controlled conditions, and they are publicly available for downloading. They represent one of three classes: car accelerating, decelerating, or maintaining constant speed. We used SVM, random forests, and artificial neural networks as classifiers, as well as the time series based approach. We also tested several approaches to audio data representation, namely: average values of basic audio features within the analyzed time segment, parametric description of the time evolution of these features, and parametric description of curves (lines) in the spectrogram. Additionally, the combinations of these representations were used in classification experiments. As a final step, we constructed an ensemble classifier, consisting of the best models. The proposed solution achieved an accuracy of almost 95%, without mistaking acceleration with deceleration, and very rare mistakes between stable speed and speed changes. The outcomes of this work can become a basis for campaigns aiming at improving traffic safety.

A novel elastic hydroxyapatite-based composite of high surgical handiness has been developed. Its potential application in orthopedics as a filler of bone defects has been studied. The biomaterial was composed of carbonated hydroxyapatite (CHAP) granules and polysaccharide polymer (β-1,3-glucan). Cylinders of 4mm in diameter and 6mm in length were implanted into bone cavities created in the proximal metaphysis of tibiae of 24 New Zealand white rabbits. 18 sham-operated animals were used as controls. After 1, 3 or 6 months, the rabbits were euthanized, the bones were harvested and subjected to analysis. Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. Peripheral quantitative computed tomography (pQCT) indicated the stimulating effect of the biomaterial on bone formation and mineralization. Densitometry (DXA) analysis suggested that biomineralization of bones was preceded by bioresorption and gradual disappearance of porous ceramic granules. The findings suggest that the CHAP-glucan composite material enables regeneration of bone tissue and could serve as a bone defect filler., (Copyright © 2015 Elsevier B.V. All rights reserved.)