Increased plasma concentration of trimethylamine N-oxide (TMAO), a proatherogenic metabolite, has been linked to adverse cardiovascular outcomes; however, it remains unclear whether TMAO is a biomarker or whether it induces direct detrimental cardiovascular effects. Because altered cardiac energy metabolism and mitochondrial dysfunction play crucial roles in the development of cardiovascular diseases, we hypothesized that increased TMAO concentration may alter mitochondrial energy metabolism. The aim of the present study was to determine the effects of TMAO on cardiac mitochondrial energy metabolism. Acute exposure of cardiac fibers to TMAO decreased LEAK (substrate-dependent) and OXPHOS (oxidative phosphorylation-dependent) mitochondrial respiration with pyruvate and impaired substrate flux via pyruvate dehydrogenase. The administration of TMAO at a dose of 120mg/kg for 8 weeks increased TMAO concentration in plasma and cardiac tissues 22-23 times to about 15μM and 11nmol/g, respectively. Long-term TMAO administration decreased mitochondrial LEAK state respiration with pyruvate by 30% without affecting OXPHOS state respiration. However, no significant changes in mitochondrial reactive oxygen species production were observed after acute exposure of cardiac fibers to TMAO under physiological conditions. In addition, both long-term TMAO administration and acute exposure to TMAO decreased respiration with palmitoyl-CoA indicating impaired β-oxidation. Taken together, our results demonstrate that increased TMAO concentration impairs pyruvate and fatty acid oxidation in cardiac mitochondria. Thus, the accumulation of TMAO in cardiac tissues leads to disturbances in energy metabolism that can increase the severity of cardiovascular events.

Background and Objectives: A particular problem in cardiology is poor adherence to pharmacological treatment among patients with hypertension. It is known that approximately half of these patients do not use their medications as prescribed by their doctor. Patients may choose not to follow the doctor’s recommendations and regularly do not control their blood pressure, owing to many factors. A convenient method for measuring the level of adherence is the Morisky Medication Adherence Scale, which also provides insight into possible remedies for low adherence. We investigated their therapy, knowledge about the disease and its control, and demographic differences to assess the adherence of patients with hypertension. Materials and Methods: This was a cross-sectional observational study. Data were collected through a survey of 12 pharmacies in Latvia. The study involved 187 participants with hypertension. Results: The prevalence of non-adherence was 46.20% in Latvia. The oldest patients were the most adherent (p = 0.001, β = 0.27). The higher the self-rated extent from 0 to 10, to which the patient takes their antihypertensives exactly as instructed by their physician, the higher the level of adherence (p < 0.0001, β = 0.38), where at “0”, the patient does not follow physician instructions at all, and at “10”, the patient completely follows the physician’s instructions. Non-adherent patients tend to assess their medication-taking behavior more critically than adherent patients. The longer the patient is known to suffer from hypertension, the more adherent he or she is (p = 0.014, β = 0.19). Conclusions: Medication non-adherence among patients with hypertension is high in Latvia. Further investigations are needed to better understand the reasons for this and to establish interventions for improving patient outcomes.

The growing market of herbal medicines, the increase in international trade in Latvia, and the lack of adequate analytical methods have raised the question of the potential use of herbal fingerprinting methods. In this study, high-performance liquid chromatography (HPLC) and thin layer chromatography (TLC) methods were developed for obtaining chromatographic fingerprints of four taxonomically and evolutionary different medicinal plants (Hibiscus sabdariffa L., Calendula officinalis L., Matricaria recutita L., Achillea millefolium L.). Retention time shifting, principal component analysis (PCA), hierarchical cluster analysis (HCA), and orthogonal projections to latent structures (OPLS) analysis were used to improve and analyze the obtained fingerprints. HPLC data detection at 270 nm was determined superior to 360 nm for the distinction of medicinal plants and used data alignment method significantly increased similarity between samples. Analyzed medicinal plant extracts formed separate, compact clusters in PCA, and the results of HCA correlated with the evolutionary relationships of the analyzed medicinal plants. Herbal fingerprinting using chromatographic analysis coupled with multivariate analysis has a great potential for the identification of medicinal plants as well as for the distinction of Latvian native medicinal plants.

Over the past two decades, hydrogels have come to the forefront of tissue engineering and regenerative medicine due to their biocompatibility, tunable degradation and low immunogenicity. Due to their porosity and polymeric network built up, it is possible to incorporate inside drugs, bioactive molecules, or other biochemically active monomers. Among biopolymers used for the fabrication of functional hydrogels, silk fibroin (SF) has received considerable research attention owing to its known biocompatibility and tunable range of mechanical properties. However, its relatively simple structure limits the potential usability. One of the emerging strategies is a chemical functionalization of SF, allowing for the introduction of methacrylate groups. This allows the versatile processing capability, including photo-cross-linking, which makes SF a useful polymer as a bioink for 3D printing. The methacrylation reaction has been done using numerous monomers such as methacrylic anhydride (MA), 2-isocyanatoethyl methacrylate (IEM), or glycidyl methacrylate (GMA). In this Review, we summarize the chemical functionalization strategies of SF materials and their resulting physicochemical properties. More specifically, a brief explanation of the different functionalization methods, the cross-linking principles, possibilities, and limitations of methacrylate compound functionalization are provided. In addition, we describe types of functional SF hydrogels and link their design principles to the performance in applications in the broad fields of biofabrication, tissue engineering, and regenerative medicine. We anticipate that the provided guidelines will contribute to the future development of SF hydrogels and their composites by providing the rational design of new mechanisms linked to the successful realization of targeted biomedical application.