Prebiotics, Probiotics, Synbiotics, Paraprobiotics and Postbiotic Compounds in IBD

The increasing incidence of inflammatory bowel diseases (IBD) and the increasing severity of the course of these diseases create the need for developing new methods of therapy. The gut microbiome is extensively studied as a factor influencing the development and course of IBD. The composition of intestinal microbiota can be relatively easily modified by diet (i.e., prebiotics, mainly dietary fibers) and bacterial supplementation using beneficial bacteria strains called probiotics. Additionally, the effects of the improved microbiome could be enhanced or gained by using paraprobiotics (non-viable, inactivated bacteria or their components) and/or postbiotics (products of bacterial metabolism or equal synthetic products that beneficially modulate immunological response and inflammation). This study summarizes the recent works on prebiotics, probiotics, synbiotics (products merging pre- and probiotics), paraprobiotics and postbiotics in IBD

Neuroprotective acitvity of AMPA-receptor antagonists

Wolne rodniki tlenowe powstają w czasie stresu oksydacyjnego, kiedy mechanizmy obronne organizmu zawodzą, Stres oksydacyjny pojawia się w przebiegu chorób neurodegeneracyjnych, m.in. w chorobie Alzheimera, chorobie Parkinsona. Niektóre zmiany neurodegeneracyjne mogą być zahamowane przez podanie antagonistów receptora AMPA. Celem niniejszej pracy, jest poszukiwanie ligandów nakierowanych na wiele celów (Multi-Target-Directed Ligands) mogących znaleźć zastosowanie w skutecznej terapii chorób neurodegeneracyjnych dzięki połączeniu działania antagonistycznego wobec receptorów AMPA z potencjałem neuroprotekcyjnym.W tym celu wybrano 4 związki, z grupy pochodnych fenyloalaniny, o znanymna podstawie wcześniejszych badań, silnym potencjalne antyoksydacyjnym, oraz udowodnionym antagonizmie wobec receptora AMPA. W ramach pracy, postanowiono dołączyć do badanych związków salsolinol i melatoninę, jako związki o oczekiwanej na podstawie doniesień literaturowych aktywności neuroprotekcyjnej i antyoksydacyjnej.Do badań potencjalnej aktywności neuroprotekcyjnej in vitro użyto dwóch ludzkich linii komórkowych neuroblastoma: IMR-32 oraz SH-SY5Y. Zastosowano również testy do pomiaru żywotności: kolorymetryczny MTS, fluorescencyjny LDH oraz test ROS - do pomiaru stresu oksydacyjnego w komórkach. Jako toksyn użyto 6-hydroksydopaminy oraz nadtlenku wodoru. Na podstawie otrzymanych wyników stwierdzono brak toksyczności związków ES 13-19, 13-22, 13-25 oraz salsolinolu wobec badanych linii komórkowych. Wykazano natomiast aktywność antyproliferacyjną związku ES 13-24. Kolejne testy mające na celu określenie neuroprotekcji badanych związków z użyciem 6-hydroksydopaminy, wykazały istotnie statystyczną neuroprotekcję neuronów przez związek ES 13-25 oraz salsolinol. W teście ROS, najlepsze okazały się być ES 13 24, ES 13-25 oraz salsolinol, natomiast brak działania neuroprotekcyjnego wykazała melatonina. Ostatni z zaplanowanych testów polegał na 24 godzinnej inkubacji komórek ze badanymi związkami wraz z H2O2, w którym potwierdzono silną neuroprotekcję salsolinolu.Free oxygen radicals are created during oxygen stress, if antioxidant’s defense system failed. Oxygen stress appears in course of the neurodegeneration diseases such as, Alzheimer’s disease and Parkinson disease. Some neurodegeneration changes can be stopped by AMPA receptor’s antagonists.The aim of this study is the search on Multi-Target-Directed Ligands (MTDL’s), which could be used in the effective therapy of neurodegenerative diseases, by combining the AMPA antagonism with the neuroprotective activity. For this purpose 4 compounds, the phenylalanine derivatives with determined in the previous studies AMPA antagonistic activity and antioxidant potential have been chosen. Additionally, salsolinol and melatonin, compounds with described in the literature neuroprotective and antioxidant activity, have been included.The human neuroblastoma cells lines IMR-32 and SH-SY5Y were used for the determination of compounds’ neuroprotective activity. Cells’ viability were measured by colorimetric MTS and fluorometric LDH tests. The fluorometric ROS-test was also used to measure the oxidative stress in cells. The selected toxins were 6-hydroxydopamine and hydrogen peroxide. As results no toxicity of compounds ES 13-19, 13-22, 13-25 and salsolinol was shown. However, the anti-proliferative effect for ES 13-24 was determined. In the neuroprotective tests with use of 6-hydroxydopamine the statistically significant neuroprotection of cells for ES 13-25 and salsolinol was shown. In the ROS-test the best activity was estimated for ES 13-24, 13-25, salsolinol and no neuroprotective activity of melatonin was found.In the last planned test, which was the 24h incubation of cells with tested compounds and H2O2, the statistically significant neuroprotection was shown for salsolinol

A New Perspective on the Renin-Angiotensin System

Cardiovascular disease (CVD) is the leading cause of death in the world. Hypertension is a serious medical problem not only in adults but also in children and adolescents. The renin-angiotensin-aldosterone system (RAAS) is one of the most important mechanisms regulating blood pressure and the balance of water and electrolytes. According to the latest reports, RAAS acts not only on endocrine but also on paracrine, autocrine, and intracrine. Moreover, RAAS has a component associated with hypotension and cardioprotective effects. These components are called alternative pathways of RAAS. The most important peptide of the alternative pathway is Ang 1–7, which is related to the Mas receptor. Mas receptors have widely known antihypertension properties, including vasodilatation, the release of nitric oxide, and increased production of anti-inflammatory cytokines. Another interesting peptide is angiotensin A, which combines the properties of the classical and alternative pathways. No less important components of RAAS are the proteolytic enzymes angiotensin convertase enzyme type 1 and 2. They are responsible for the functioning of the RAAS system and are a hypertension therapeutic target. Also involved are tissue-specific enzymes that form a local renin-angiotensin system. Currently, a combination of drugs is used in hypertension treatment. These drugs have many undesirable side effects that cannot always be avoided. For this reason, new treatments are being sought, and the greatest hope comes from the ACE2/ang 1–7/MasR axis

A New Perspective on the Renin-Angiotensin System

Cardiovascular disease (CVD) is the leading cause of death in the world. Hypertension is a serious medical problem not only in adults but also in children and adolescents. The renin-angiotensin-aldosterone system (RAAS) is one of the most important mechanisms regulating blood pressure and the balance of water and electrolytes. According to the latest reports, RAAS acts not only on endocrine but also on paracrine, autocrine, and intracrine. Moreover, RAAS has a component associated with hypotension and cardioprotective effects. These components are called alternative pathways of RAAS. The most important peptide of the alternative pathway is Ang 1–7, which is related to the Mas receptor. Mas receptors have widely known antihypertension properties, including vasodilatation, the release of nitric oxide, and increased production of anti-inflammatory cytokines. Another interesting peptide is angiotensin A, which combines the properties of the classical and alternative pathways. No less important components of RAAS are the proteolytic enzymes angiotensin convertase enzyme type 1 and 2. They are responsible for the functioning of the RAAS system and are a hypertension therapeutic target. Also involved are tissue-specific enzymes that form a local renin-angiotensin system. Currently, a combination of drugs is used in hypertension treatment. These drugs have many undesirable side effects that cannot always be avoided. For this reason, new treatments are being sought, and the greatest hope comes from the ACE2/ang 1–7/MasR axis

Prebiotics, probiotics, synbiotics, paraprobiotics and postbiotic compounds in IBD

The increasing incidence of inflammatory bowel diseases (IBD) and the increasing severity of the course of these diseases create the need for developing new methods of therapy. The gut microbiome is extensively studied as a factor influencing the development and course of IBD. The composition of intestinal microbiota can be relatively easily modified by diet (i.e., prebiotics, mainly dietary fibers) and bacterial supplementation using beneficial bacteria strains called probiotics. Additionally, the effects of the improved microbiome could be enhanced or gained by using paraprobiotics (non-viable, inactivated bacteria or their components) and/or postbiotics (products of bacterial metabolism or equal synthetic products that beneficially modulate immunological response and inflammation). This study summarizes the recent works on prebiotics, probiotics, synbiotics (products merging pre- and probiotics), paraprobiotics and postbiotics in IBD

Prebiotics, Probiotics, and Postbiotics in the Prevention and Treatment of Anemia

Iron deficiency anemia (IDA) is very common and affects approximately 1/3 of the world’s human population. There are strong research data that some probiotics, such as Lactobacillus acidophilus and Bifidobacterium longum improve iron absorption and influence the course of anemia. Furthermore, prebiotics, including galactooligosaccharides (GOS) and fructooligosaccharides (FOS), increase iron bioavailability and decrease its destructive effect on the intestinal microbiota. In addition, multiple postbiotics, which are probiotic metabolites, including vitamins, short-chain fatty acids (SCFA), and tryptophan, are involved in the regulation of intestinal absorption and may influence iron status in humans. This review presents the actual data from research studies on the influence of probiotics, prebiotics, and postbiotics on the prevention and therapy of IDA and the latest findings regarding their mechanisms of action. A comparison of the latest research data and theories regarding the role of pre-, post-, and probiotics and the mechanism of their action in anemias is also presented and discussed

Phenylalanine-based AMPA receptor antagonist as the anticonvulsant agent with neuroprotective activity - in vitro and in vivo studies

Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants 1 and 8 were further examined to evaluate their neuroprotective properties in vitro. In this study, compound 1 showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Both compounds also showed prevention from high levels of reactive oxygen species (ROS) in SH-SY5Y cells. Furthermore, the desired monoamine oxidase B (MAO-B) inhibition effect (IC50 = 278 ± 29 nM) for 1 was determined. No toxic effects up to 100 µM of 1 and 8 against neuroblastoma cells were observed. Furthermore, in vivo studies showed that compound 1 demonstrated significant anticonvulsant potential in 6-Hz test, but in neuropathic pain models its antiallodynic and antihyperalgesic properties were not observed. Concluding, the compound 1 seems to be of higher importance as a new phenylalanine-based lead candidate due to its confirmed promise in in vitro and in vivo anticonvulsant activity

Measurement of Dijet Production at Low Q2Q^{2} at HERA

The analyses of jet production in various high energy processes have become a major field for testing perturbative QCD. In the case of electron-proton collisions, investigated in the thesis, the jet cross sections are successfully described in most of the HERA kinematic range by next-to-leading (NLO) QCD calculations. However, regions of phase space have previously been identified where NLO predictions do not reproduce the data satisfactorily. The presented analysis describes a new measurement of the dijet cross sections together with detailed comparisons of the data with available perturbative QCD calculations in order to identify which of them describe the data in which region. Doing that we use NLO QCD calculations as well as LO calculations supplemented with parton showers, which take into account leading logarithmic contributions to all orders.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi