The Involvement of the Endogenous Opioid System in the Gastrointestinal Aging in Mice and Humans

Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.     

The Effect of the Topmost Layer and the Type of Bone Morphogenetic Protein-2 Immobilization on the Mesenchymal Stem Cell Response

Recombinant human bone morphogenetic protein-2 (rhBMP-2) plays a key role in the stem cell response, not only via its influence on osteogenesis, but also on cellular adhesion, migration, and proliferation. However, when applied clinically, its supra-physiological levels cause many adverse effects. Therefore, there is a need to concomitantly retain the biological activity of BMP-2 and reduce its doses. Currently, the most promising strategies involve site-specific and site-directed immobilization of rhBMP-2. This work investigated the covalent and electrostatic binding of rhBMP-2 to ultrathin-multilayers with chondroitin sulfate (CS) or diazoresin (DR) as the topmost layer. Angle-resolved X-ray photoelectron spectroscopy was used to study the exposed chemical groups. The rhBMP-2 binding efficiency and protein state were studied with time-of-flight secondary ion mass spectrometry. Quartz crystal microbalance, atomic force microscopy, and enzyme-linked immunosorbent assay were used to analyze protein–substrate interactions. The effect of the topmost layer was tested on initial cell adhesion and short-term osteogenesis marker expression. The results show the highest expression of selected osteomarkers in cells cultured on the DR-ended layer, while the cellular flattening was rather poor compared to the CS-ended system. rhBMP-2 adhesion was observed only on negatively charged layers. Cell flattening became more prominent in the presence of the protein, even though the osteogenic gene expression decreased.     

The Influence of Exogenous Jasmonic Acid on the Biosynthesis of Steroids and Triterpenoids in Calendula officinalis Plants and Hairy Root Culture

The interplay between steroids and triterpenoids, compounds sharing the same biosynthetic pathway but exerting distinctive functions, is an important part of the defense strategy of plants, and includes metabolic modifications triggered by stress hormones such as jasmonic acid. Two experimental models, Calendula officinalis hairy root cultures and greenhouse cultivated plants (pot plants), were applied for the investigation of the effects of exogenously applied jasmonic acid on the biosynthesis and accumulation of steroids and triterpenoids, characterized by targeted GC-MS (gas chromatography-mass spectroscopy) metabolomic profiling. Jasmonic acid elicitation strongly increased triterpenoid saponin production in hairy root cultures (up to 86-fold) and their release to the medium (up to 533-fold), whereas the effect observed in pot plants was less remarkable (two-fold enhancement of saponin biosynthesis after a single foliar application). In both models, the increase of triterpenoid biosynthesis was coupled with hampering the biomass formation and modifying the sterol content, involving stigmasterol-to-sitosterol ratio, and the proportions between ester and glycoside conjugates. The study revealed that various organs in the same plant can react differently to jasmonic acid elicitation; hairy root cultures are a useful in vitro model to track metabolic changes, and enhanced glycosylation (of both triterpenoids and sterols) seems to be important strategy in plant defense response.     

The Role of Epigenetics in Neuroinflammatory-Driven Diseases

Neurodegenerative disorders are characterized by the progressive loss of central and/or peripheral nervous system neurons. Within this context, neuroinflammation comes up as one of the main factors linked to neurodegeneration progression. In fact, neuroinflammation has been recognized as an outstanding factor for Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple sclerosis (MS). Interestingly, neuroinflammatory diseases are characterized by dramatic changes in the epigenetic profile, which might provide novel prognostic and therapeutic factors towards neuroinflammatory treatment. Deep changes in DNA and histone methylation, along with histone acetylation and altered non-coding RNA expression, have been reported at the onset of inflammatory diseases. The aim of this work is to review the current knowledge on this field.     

Changes in Polychlorinated Biphenyl Residues in Milk during Lactation: Levels of Contamination,Influencing Factors,and Infant Risk Assessment

Given the importance of breastfeeding infants, the contamination of human milk is a significant public concern. The aim of this study was to assess the contamination of human milk with dioxin-like PCBs (dl-PCBs) and non-dioxin-like PCBs (ndl-PCBs) in relation to the duration of lactation and other influencing factors, especially the frequency of the consumption of selected foods during pregnancy. Based on this, the health risk to infants was assessed and compared to the tolerable daily intake (TDI). PCB determinations were performed using gas chromatography/mass spectrometry. The ∑ndl-PCB content ranged from 0.008 to 0.897 ng/g w.w., at an average of 0.552 ng/g wet weight, which was 55% of the maximum level according to the EU guidelines for foods for infants and young children. The toxic equivalent (TEQ) was in the range of 0.033–5.67 pg-TEQ/g w.w. The content of non-ortho, mono-ortho, and ndl-PCBs in human milk decreased the longer lactation continued. Moreover, when pregnant women smoked tobacco, this correlated significantly with increases in the concentrations of PCB congeners 156, 118, and 189 in human milk. The human milk contents of PCB congeners 77, 81, 186, 118, and 189 were strongly positively correlated with the amount of fish consumed. The content of stable congeners PCB 135 and PCB 153 increased with age.     

Novel Arylpiperazine Derivatives of Salicylamide with α1-Adrenolytic Properties Showed Antiarrhythmic and Hypotensive Properties in Rats

Cardiovascular diseases remain one of the leading causes of death worldwide. Unfortunately, the available pharmacotherapeutic options have limited effectiveness. Therefore, developing new drug candidates remains very important. We selected six novel arylpiperazine alkyl derivatives of salicylamide to investigate their cardiovascular effects. Having in mind the beneficial role of α₁-adrenergic receptors in restoring sinus rhythm and regulating blood pressure, first, using radioligand binding assays, we evaluated the affinity of the tested compounds for α-adrenergic receptors. Our experiments revealed their high to moderate affinity for α₁- but not α₂-adrenoceptors. Next, we aimed to determine the antiarrhythmic potential of novel derivatives in rat models of arrhythmia induced by adrenaline, calcium chloride, or aconitine. All compounds showed potent prophylactic antiarrhythmic activity in the adrenaline-induced arrhythmia model and no effects in calcium chloride- or aconitine-induced arrhythmias. Moreover, the tested compounds demonstrated therapeutic antiarrhythmic activity, restoring a normal sinus rhythm immediately after the administration of the arrhythmogen adrenaline. Notably, none of the tested derivatives affected the normal electrocardiogram (ECG) parameters in rodents, which excludes their proarrhythmic potential. Finally, all tested compounds decreased blood pressure in normotensive rats and reversed the pressor response to methoxamine, suggesting that their hypotensive mechanism of action is connected with the blockade of α₁-adrenoceptors. Our results confirm the antiarrhythmic and hypotensive activities of novel arylpiperazine derivatives and encourage their further investigation as model structures for potential drugs.     

Zingiber officinale Rosc. in the Treatment of Metabolic Syndrome Disorders—A Review of In Vivo Studies

Inflammation is a protective reaction of the innate immune system as a response to imbalances caused by a specific stimulus, a disease or a pathogen. A prolonged inflammatory condition may lead to the development of metabolic syndrome, which affects more than one-fourth of the world’s population. This condition leads to the development of multi-organ disorders based on disrupted blood lipid and sugar levels, hypertension and oxidative stress. The review aims to present Zingiber officinale Rosc. as a plant that exhibits a variety of healing properties and restores the organism’s equilibrium. Ginger (GI) rhizomes have been commonly used in traditional medicine to treat arthritis, stomach ache, nonalcoholic fatty liver disease, rheumatism, nervous system syndromes, asthma, diabetes and nausea caused by pregnancy or chemotherapy. This review gathers together data from in vivo experiments related to the application of ginger for the treatment of inflammatory conditions, obesity, diabetes and other related disorders as a consequence of metabolic syndrome, including the confirmed molecular mechanisms of action.     

Assessing the effectiveness of colloidal microcrystalline cellulose as a suspending agent for black and white liquid dyes

This study aimed to determine the effect of the concentration (1, 5, or 8 wt%) of colloidal microcrystalline cellulose (MCCS) as suspending agent on the long-term stability and rheology of the vegetable carbon (C) and calcium carbonate (CC) suspended in water–glycerine mixture. These suspensions as ready-to-use black and white liquid dyes containing 10 wt% C or CC were assessed for particle size, Turbiscan stability index (TSI), steady shear, thixotropy and dynamic viscoelasticity. After 370 days, the black dyes showed excellent stability (TSI ≪ 0.5) at 4 °C and 25 °C already at 1 wt% MCCS, while the white dyes showed reasonable stability (TSI 1–3) only at 5 and 8 wt% MCCS. Dye formulations exhibited a relatively liquid-like viscoelastic behaviour, while they showed extremely shear-thinning behaviour with a network structure dependent on the concentration of the MCCS as exhibited by the increase in thixotropy and the existence of the measurable yield stress.