Classical and Alternative Pathways of the Renin-Angiotensin-Aldosterone System in Regulating Blood Pressure in Hypertension and Obese Adolescents.

Primary hypertension (PH) is the leading form of arterial hypertension (AH) in adolescents. Hypertension is most common in obese patients, where 20 to 40% of the population has elevated blood pressure. One of the most effective mechanisms for regulating blood pressure is the renin-angiotensin-aldosterone system (RAAS). The new approach to the RAAS talks about two opposing pathways between which a state of equilibrium develops. One of them is a classical pathway, which is responsible for increasing blood pressure and is represented mainly by the angiotensin II (Ang II) peptide and, to a lesser extent, by angiotensin IV (Ang IV). The alternative pathway is responsible for the decrease in blood pressure and is mainly represented by angiotensin 1-7 (Ang 1-7) and angiotensin 1-9 (Ang 1-9). Our research study aimed to assess changes in angiotensin II, angiotensin IV, angiotensin 1-7, and angiotensin 1-9 concentrations in the plasma of adolescents with hypertension, with hypertension and obesity, and obesity patients. The Ang IV concentration was lower in hypertension + obesity versus control and obesity versus control, respectively p = 0.01 and p = 0.028. The Ang 1-9 concentration was lower in the obesity group compared to the control group (p = 0.036). There were no differences in Ang II and Ang 1-7 peptide concentrations in the hypertension, hypertension and obesity, obesity, and control groups. However, differences were observed in the secondary peptides, Ang IV and Ang 1-9. In both cases, the differences were related to obesity.

Endogenous Opioids in Crohn's Disease.

Caring for patients with Crohn's disease (CD) is a serious challenge in modern medicine. The increasing incidence of CD among adolescents and the severe course of the disease create the need for new methods of diagnosis and therapy. Endogenous opioids are a group of low molecular weight chemical compounds with analgesic and anti-inflammatory properties. Endorphins, enkephalins, and dynorphins may have potentially beneficial effects on the course of CD. Previous research data on this topic are inconsistent. Some authors have reported an increase in the concentration of leukocytes during the course of inflammatory bowel disease (IBD) while others have described a downward trend, explained by DPP-IV enzyme activity. Even fewer data are available on plasma endo-opioid level. There is also a lack of comprehensive studies that have assessed the endo-opioid system in patients with IBD. Therefore, the objective of this study was to measure the serum concentrations of human ß-endorphin, human proenkephalin (A), and human big dynorphin in CD patients in the acute phase of the disease, during hospital treatment, and in the remission state. All determinations were performed using ELISA kits. The results of our study showed that the concentrations of all the tested endo-opioids, especially ß-endorphin and proenkephalin (A), were reduced in adolescents with CD compared to those in the healthy control group, during the acute phase of the disease, and in the remission state. Modulation of the endogenous opioid system and the use of selective nonnarcotic agonists of opioid receptors seems to be promising goals in the future treatment of CD.

Prevention and Health Benefits of Prebiotics, Probiotics and Postbiotics in Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children, comprising 75-85% of cases. Aggressive treatment of leukemias includes chemotherapy and antibiotics that often disrupt the host microbiota. Additionally, the gut microbiota may play a role in the development and progression of acute leukemia. Prebiotics, probiotics, and postbiotics are considered beneficial to health. The role of prebiotics in the treatment and development of leukemia is not well understood, but inulin can be potentially used in the treatment of leukemia. Some probiotic bacteria such as Lactobacillus shows anticancer activity in in vitro studies. Additionally, Bifidobacterium spp., as a consequence of the inhibition of growth factor signaling and mitochondrial-mediated apoptosis, decrease the proliferation of cancer cells. Many bacterial metabolites have promising anticancer potential. The available research results are promising. However, more research is needed in humans, especially in the child population, to fully understand the relationship between the gut microbiota and acute leukemia.

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.

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.

Salsolinol-neurotoxic or Neuroprotective?

Salsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline), widely available in many edibles, is considered to alter the function of dopaminergic neurons in the central nervous system and thus, multiple hypotheses on its either physiological and/or pathophysiological role have emerged. The aim of our work was to revisit its potentially neurotoxic and/or neuroprotective role through a series of both in vitro and in vivo experiments. Salsolinol in the concentration range 10-250 µM did not show any significant release of lactate dehydrogenase from necrotic SH-SY5Y cells and was able in the concentration of 50 and 100 µM to rescue SH-SY5Y cells from death induced by H2O2. Its neuroprotective effect against neurotoxin 6-hydroxydopamine was also determined. Salsolinol was found to decrease significantly the reactive oxygen species level in SH-SY5Y cells treated by 500 µM H2O2 and the caspase activity induced by 300 µM of H2O2 or 100 µM of 6-hydroxydopamine. Serum levels of TNFα and CRP of salsolinol-treated rats were not significantly different from control animals. Both TNFα and CRP served as indirect markers of neurotoxicity and/or neuroprotection. Although the neurotoxic properties of salsolinol have numerously been emphasized, its neuroprotective properties should not be neglected and need greater consideration.