The immune system protects the body from infectious agents such as bacteria, viruses, or fungi. Once encountered with pathogens or antigens, the innate and adaptive arms of the immune system trigger a strong immune response to eliminate them from the system and protect the body. Thus, well-balanced immunity is pivotal for maintaining human health, as an insufficient level of immune defense leads to infections and tumors. In contrast, the excessive functioning of the immune system causes the development of autoimmune diseases and allergies. Strong immunity requires adequate nutrition, dietary interventions, and sufficient intake of certain vitamins (vitamin C, vitamin D, and folic acid) and minerals (magnesium, zinc, and selenium). Therefore, nutritional and micronutrient deficiencies lead to compromised immunity. Several natural ingredients have shown potent immunomodulatory properties. The immune-enhancing properties of many plants and fungi are due to containing bioactive phytoconstituents such as polyphenols, terpenoids, β-glucans, vitamins, etc. Probiotics and prebiotics can be used as innovative tools to reduce intestinal inflammation and downregulate hypersensitivity reactions. Plant sources of melatonin, a multifunctional molecule with proven anti-inflammatory and immunomodulatory properties, have been discovered relatively recently. The bioactive compounds augment the immune response by directly increasing the cytotoxic activity of natural killer cells, macrophages, and neutrophils. Many phytoconstituents prevent cell damage due to their powerful antimicrobial, antioxidant, and anti-inflammatory properties. The present review attempts to understand the molecular mechanisms underlying the immune-enhancing properties of some bioactive compounds from plants, fungi, animals, microorganisms, and other natural sources.

Cardiovascular complications are the most prevalent cause of morbidity and mortality in diabetic patients. Metformin is currently the first-line blood glucose-lowering agent with potential relevance to cardiovascular diseases. However, the underpinning mechanisms of action remain elusive. Here, we report that metformin represses cardiac apoptosis at least in part through inhibition of the FoxO1 pathway. In a mouse model of ischemia-reperfusion (I/R), treatment with metformin attenuated I/R-induced cardiac and hypertrophic remodeling after 14 days of post-reperfusion. Additionally, cardiac expression of brain-like natriuretic peptide (BNP) was significantly reduced in metformin-treated mice after 14 days of cardiac I/R. In cultured H9C2 cells, metformin counteracted hypertrophic and apoptotic responses to metabolic or hypoxic stress. FoxO1 silencing by siRNA abolished anti-apoptotic effect of metformin under hypoxic stress in H9C2 cells. Taken together, these results suggest that metformin protects the heart against hypertrophic and apoptotic remodeling after myocardial infarction.

Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley male rats were split into three equal groups and given carbon tetrachloride (CCl₄), 2 g/kg (CCl₄ group) or the same dose of CCl₄ and melatonin, 10 mg/kg (CCl₄/melatonin group) or saline (control group). The effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in serum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in all three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine and thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in serum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations were decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate dehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum: NO₂-by 37.9%; NO₃-by 29.2%. There was no significant difference in content NO₂-in the liver, but concentration of NO₃-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both in serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in serum, nor in liver. The histopathological liver lesions observed in the CCl₄/melatonin group were less severe than those seen in the CCl₄ group. Conclusions: we demonstrated an ameliorating effect of melatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and histopathological lesions in the liver in rats with CCl₄-induced hepatitis.

Objectives: The need for improving healthcare decision making by implementing health technology assessment (HTA) has been a top priority in Ukraine since 2016. This study sought to provide a tailor-made HTA implementation roadmap, drawing on insights from national stakeholders.Methods: We conducted a survey using a questionnaire already applied in previous HTA research. We assessed the status of HTA when reforms were initiated in 2016 and examined perspectives on possible future developments among policy makers and representatives of pharmaceutical companies and patient organizations.Results: Thirty-two respondents answered the survey. Forty-eight percent of respondents were not aware of HTA training in Ukraine, but 91 percent preferred having either a graduate or postgraduate training. Experts stated that funding for HTA research and for critical appraisal of HTA submissions was limited, but in the future, they would increase funding mainly from public sources. A public HTA agency with academic support was the most preferred organizational structure. Eighty-eight percent of respondents opted for full transparency, making the HTA agency's recommendations and the related appraisal reports publicly available. A great majority of participants preferred mandating the use of local data in certain categories and indicated the importance of evaluating the transferability of international evidence. Healthcare priority and cost-effectiveness were the most important criteria for decisions, applied with a soft explicit threshold.Conclusions: Ukraine is in the early phase of implementing HTA and our study provides a clear vision of national stakeholders about the future directions. In addition, learning from the experiences of other countries may help the implementation process.

The use of plant raw materials is one of the areas of modern pharmaceutical science in the production of herbal drugs. The genus Epilobium counts more than 200 species, many species of which are used in traditional medicine. Among the Epilobium species, Epilobium angustifolium is one of the well-known medicinal plants which have been used worldwide in habitual medicine. There is insufficient information in the literature on the biologically active substances of Epilobium angustifolium L. The presence of three major polyphenol groups: phenolic acids, flavonoids, and ellagitannins were identified in E. angustifolium extracts. Traditionally, the infusion of leaves of this plant could be useful for headaches, cold and gastrointestinal disorder. The Epilobium angustifolium L. as an insufficiently studied plant is a promising object of study, including amino acids composition. To assess the relationship between the production of primary metabolites and their possible therapeutic properties, we analyzed the amino acid profile of the plant Epilobium angustifolium used in traditional medicine. The study of compounds generated by plants as a result of defense mechanisms permits an understanding of the molecular mechanism involved in their medicinal properties. The aim. Thus, the aim of the study was to conduct an HPLC analysis of the amino acids of E. angustifolium to establish the prospects for the use of the raw materials in medical and pharmaceutical practice. The results of the current study will be used in further breeding programs aimed to obtain an industrial form of E. angustifolium suitable for pharmaceutical and food applications. Materials and methods. The determination of amino acids composition of Epilobium angustifolium was conducted using Agilent 1200 (Agilent Technologies, USA). Results. The HPLC method identified sixteen free amino acids and seventeen bound amino acids in the Epilobium angustifolium herb. The studies have shown that Epilobium angustifolium L. herb is mainly composed of free amino acids such as L-phenylalanine (1.65 µg/mg), L-glutamic acid (1.51 µg/mg), L-arginine (1.24 µg/mg), L-alanine (0.98 µg/mg) and L-aspartic acid (0.57 µg/mg), which were presents in the greatest amount. The dominant bound amino acids in the studied raw material were L-glutamic acid, L-aspartic acid, L-leucine, and L-alanine, the content of which was 32.37 µg/mg, 10.59 µg/mg, 8.70 µg/mg, and 6.22 µg/mg respectively. Conclusions. Using the HPLC method determined the amino acids in the herb of Epilobium angustifolium L. The concentrations of L-aspartic acid, L-glutamic acid, L-arginine, L-alanine and L-phenylalanine are predominate among free and bound amino acids in the Epilobium angustifolium L. herb. The result shows that Epilobium angustifolium L. is the source of amino acids, so the use of this plant raw material for new remedies is possible in the future

Market access for pharmaceuticals is a set of strategies, activities and processes developed by pharmaceutical companies to provide affordable medicines at appropriate fair prices in a particular health care system. Access to the pharmaceutical market covers main areas of stages, including the health technology assessment (HTA). The aim of the work was to analyze the stages of market access for pharmaceuticals in particular the implementation of HTA based on regulatory review, tasks and activities of the HTA Department of the State Expert Center of the Ministry of Health and the Expert Committee for Selection and Use of Essential Medicines and directions of HTA use in the health care system in Ukraine. Materials: legislation governing the conduction of HTA in Ukraine, international publications on the subject of the study. Research methods: system and content analysis, data synthesis and generalization of information, extrapolation, retrospective analysis. We have generalized the legislation for the introduction of HTA in Ukraine, the stages of institutionalization of the direction, the HTA roadmap, current state of financing of medicines using several regulatory lists from the perspective of state payer, including: National list of essential medicines, nomenclature of central procurement, insulin reimbursement. The mechanisms of selection of new medicines and evaluation with the use of HTA methods for inclusion on the regulatory lists, is in particular only for the National list, by criteria are presented: morbidity, disease prevalence and mortality; evidence of comparative efficacy (effectiveness), safety and cost-effectiveness; demand; the results of the budget impact analysis; pharmacokinetic properties of drugs; WHO recommendations on the use of essential medicines. In order to inform decisions on the rational allocation and use of financial resources in the health care system in January 2019, the HTA Department in Ukraine was established at SE "State Expert Center of the Ministry of Health of Ukraine" to conduct HTA and examination of applications for inclusion of medicines on National list. It is substantiated that the institutionalization of the direction with the establishment of the HTA Department is an important step in ensuring the ecosystem of decision-making based on HTA in the Ukrainian health care system. The developed methodological support, in particular the first HTA guidelines, the model of multicriteria decision analysis, experience in assessment of applications for inclusion of medicines on the National list indicate the feasibility of further expanding the use of HTA for other regulatory lists, including the list of central procurement programs and development of single positive list of medicines for public funding in Ukraine.