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Water pollution caused by anthropogenic activity is a huge environmental problem. Huge amounts of consumed medicinal substances cause them to get into the environment. Non-steroidal anti-inflammatory drugs, including ibuprofen, are one of the most popular drugs in the world. This article presents the biodegradation of ibuprofen and isopropyl ester salts of various amino acids. Twelve ibuprofen isopropyl esters of L-amino acids were used in the research. The obtained derivatives may be a safer and more effective alternative to ibuprofen. Biodegradation tests were carried out using activated sludge. Sewage sludge was obtained from the local sewage treatment plant in Szczecin "Pomorzany". Ibuprofen derivatives, ibuprofenates of isopropyl amino acid esters, were used for the tests. It was checked how the type of structural modification of ibuprofen affects the biodegradation of the drug used. In this publication, it was verified how the type of amino acid affects biodegradation. Our evaluation of the biodegradation of ibuprofen derivatives by bacterial cultures revealed that six compounds are attractive carbon and energy sources for the active material utilized. These compounds were readily biodegradable within 28 days. There were no straightforward relationships between the structure, properties, and biodegradability of the obtained derivativesWater pollution caused by anthropogenic activity is a huge environmental problem. Huge amounts of consumed medicinal substances cause them to get into the environment. Non-steroidal anti-inflammatory drugs, including ibuprofen, are one of the most popular drugs in the world. This article presents the biodegradation of ibuprofen and isopropyl ester salts of various amino acids. Twelve ibuprofen isopropyl esters of L-amino acids were used in the research. The obtained derivatives may be a safer and more effective alternative to ibuprofen. Biodegradation tests were carried out using activated sludge. Sewage sludge was obtained from the local sewage treatment plant in Szczecin "Pomorzany". Ibuprofen derivatives, ibuprofenates of isopropyl amino acid esters, were used for the tests. It was checked how the type of structural modification of ibuprofen affects the biodegradation of the drug used. In this publication, it was verified how the type of amino acid affects biodegradation. Our evaluation of the biodegradation of ibuprofen derivatives by bacterial cultures revealed that six compounds are attractive carbon and energy sources for the active material utilized. These compounds were readily biodegradable within 28 days. There were no straightforward relationships between the structure, properties, and biodegradability of the obtained derivatives

Abstract. This article presents a comprehensive study on the formulation and evaluation of pharmaceutical emulsions for topical drug delivery. The research focused on emulsions containing ibuprofen and its derivatives (sodium and L-lysine propyl ester salts), investigating their solubility, consistency, stability, and skin permeation. The study offers valuable insights into the development of effective pharmaceutical products. Background. Transdermal and topical drug delivery is a promising approach for the treatment of various medical conditions. Pharmaceutical emulsions provide an ideal platform for delivering active substances through the skin. The selection of emulsion ingredients, consistency, and stability play a critical role in determining the suitability of these formulations. Aim of the study. The primary aim of this study was to formulate and evaluate pharmaceutical emulsions containing ibuprofen and other active substances. Key objectives included assessing solubility, consistency, stability, and skin permeation characteristics of the emulsions. The study aimed to provide insights into the development of effective topical drug delivery systems. Material and methods. Solubility tests were conducted to select suitable emulsion ingredients. Various emulsions were prepared with different water-to-oil phase ratios. Rheology modifiers were added to enhance consistency. Quality control assessments were performed, including uniformity, consistency, stability, density, viscosity, and particle size analysis. The release of active substances from the formulations and their penetration and accumulation in the skin were determined. Results. The results revealed variations in viscosity, consistency, and stability among different formulations. Emulsion-based preparations demonstrated the highest accumulation of active substances in the skin, with formulation F1 (5294.617 μg/g skin) exhibiting the most promising results. The highest release of ibuprofen was observed from the formulation based on Celugel with the addition of [LysOPr][IBU] (F6) - approximately 7750 μg IBU/cm2, and the highest penetration of the active substance was obtained for the emulsion with the addition of IBU∙Na (F2) - 3300 μg IBU/cm2 after 24 hours of testing. Conclusion. This comprehensive study on pharmaceutical emulsions for topical drug delivery provides critical insights into the formulation and evaluation of cosmetic and pharmaceutical products. The findings highlight the importance of ingredient selection, consistency, and stability in the development of effective emulsion-based formulations. Furthermore, the study suggests that emulsion-based preparations have potential for topical applications, especially for more hydrophilic active substances. Future research can build on these results to enhance drug delivery systems and improve patient outcomes.

Abstract The FTO gene rs9936909 polymorphism is one of the well-documented single nucleotide polymorphisms in the context of increased risk of obesity, including in children. Few studies have tested the association of the FTO gene with cognitive functions. Deficits of “cool” executive functions (EFs) are considered a potential risk factor for excessive weight. The aims of our study were to investigate whether cool EFs are associated with the Body Mass Index, the Fat Mass Index and the risk of excess body mass and overfatness in neurotypically school-aged children, and whether the FTO gene polymorphism is involved in development of this possible association. The sample consisted of 553 children aged 6–12 years old. A body composition analysis, a neuropsychological assessment of EFs, and FTO polymorphism genotyping were performed in the children studied. The study found a significant association of an interference effect in theStroop Color-Word Interference Task and the risk of excessive body fatness, but not excessive body mass. There were no explicit associations between the FTO genotype and EFs deficits. Environmental factors, and particularly low maternal education, appeared to be the strongest contributors to the increased risk of obesity.

Alterations in brain-derived neurotrophic factor (BDNF) expression have been suggested to mediate the influence of environmental factors on the emergence of depression through epigenetic modifications. However, research on this subject in the developmental population is lacking and the pathophysiology of adolescent depression remains unclear. We aimed to investigate the alterations in BDNF expression and global DNA methylation in depression among adolescent girls. Thirty female inpatients with the initial diagnosis of depression were assessed before and after the period of antidepressant treatment and compared with thirty age-matched healthy controls. The assessment involved BDNF and proBDNF serum levels, the BDNF gene exon IV promoter methylation, and global DNA methylation. The methylation level in the BDNF gene exon IV promoter was significantly lower in the studied group compared with the control and correlated negatively with the severity of depression. The test distinguished the studied group from the controls with a sensitivity of 37% and specificity of 90%. The differences were no longer present after the period of antidepressant treatment. No differences in the global DNA methylation, BDNF, and proBDNF levels were found. We concluded that decreased methylation in the BDNF exon IV promoter could be considered as a biomarker of a depression state among adolescent girls.

Anorexia nervosa (AN) is an eating disorder characterized by restrictive eating and significant weight loss. In the course of AN, changes are observed in appetite regulation, including orexigenic ghrelin and potentially anorexigenic obestatin. The study aimed to determine if any changes in serum ghrelin and obestatin levels during treatment of AN are observed, while investigating the correlations between these peptides and the severity of disturbed eating attitudes, depression, and anxiety. Thirty adolescent inpatients with AN (examined twice: before hospitalization treatment AN-BT and after treatment AN-AT) and thirty healthy age- and height-matched girls (CG) participated in the study. Anthropometric, serum ghrelin and obestatin concentrations and psychometric evaluations (Eating Attitudes Test 26 Item-EAT-26, Beck Depression Inventory-BDI, Hamilton Depression Rating Scale-HDRS, and Yale Brown Obsessive-Compulsive Scale-Y-BOCS) were performed. The study revealed significantly higher ghrelin and obestatin levels in AN-BT than in AN-AT. A trend toward lower levels during treatment provided partial normalizations. Analyzing correlations in the AN-BT vs. CG group, correlations of peptides with EAT-26, BDI, and HDRS scores were detected. These results suggest a potential role for ghrelin and obestatin in the context of defense mechanisms regulating appetite and body weight in the course of AN and in terms of psychopathological changes co-occurring with this eating disorder.

Plain English summary The orofacial region is affected by various inflammatory and autoimmune conditions, which might translate into general and regional changes. Saliva is one of the biological fluids where biomarkers of the aforementioned conditions, including sensitivity to pain, could be detected. It is also noteworthy that anorexia nervosa (AN) and malnutrition may change the saliva's analgesic or immune content, but this scientific area is still not satisfactorily explored. The present work related to analgesic (opiorphin peptide) and anti-infectious agents (immunoglobulins Ig A, IgG, IgM) in said body fluid among 83 adolescent patients with severe AN compared to 79 healthy controls. In addition, oral hygiene levels were assessed in the oral cavity via the Plaque Control Record index (PCR). In the AN group, the concentration of opiorphin was significantly higher as compared to the control group, in contrast to IgM, which was significantly lower than in the control group. There were no notable differences in the levels of IgA and IgG between groups, despite a slightly higher concentrations of IgA in the AN group. A correlation was found between opiorphin and all immunoglobulins. A similar correlation was found between PCR index and all immunoglobulins.The present work shows how analgesic opiorphin depends on the oral inflammatory status. This might be a direction for further investigating the immune alterations in patients with AN-related malnutrition. Inclusion of AN patients in intensive oral hygiene care may also be considered.

Metabolic syndrome (MS) is a growing social, economic, and health problem. MS coexists with nearly half of all patients with affective disorders. This study aimed to evaluate the neurobiological parameters (clinical, anthropometric, biochemical, adipokines levels, and ultrasound of carotid arteries) and their relationship with the development of MS in patients with bipolar disorder. The study group consisted of 70 patients (50 women and 20 men) hospitalized due to episodes of depression in the course of bipolar disorders. The Hamilton Depression Rating Scale was used to assess the severity of the depression symptoms in an acute state of illness and after six weeks of treatment. The serum concentration of adipokines was determined using an ELISA method. The main finding of this study is that the following adipokines correlated with MS in the bipolar depression women group: visfatin, S100B, and leptin had a positive correlation, whereas adiponectin, leptin-receptor, and adiponectin/leptin ratio showed a negative correlation. Moreover, the adiponectin/leptin ratio showed moderate to strong negative correlation with insulin level, BMI, waist circumference, triglyceride level, treatment with metformin, and a positive moderate correlation with HDL. The adiponectin/leptin ratio may be an effective tool to assess MS in depressed female bipolar patients.

This study aimed to evaluate the effect of chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen [IBU] from the acrylic pressure-sensitive adhesive used as a drug-in-adhesives matrix type transdermal patch. The active substances tested were ibuprofen salts obtained by pairing the ibuprofen anion with organic cations, such as amino acid isopropyl esters. The structural modification of ibuprofen tested were Ibuprofen sodium salt, [GlyOiPr][IBU], [AlaOiPr][IBU], [ValOiPr][IBU], [SerOiPr][IBU], [ThrOiPr][IBU], [(AspOiPr)2][IBU], [LysOiPr][IBU], [LysOiPr][IBU]2, [PheOiPr][IBU], and [ProOiPr][IBU]. For comparison, the penetration of unmodified ibuprofen and commercially available patches was also investigated. Thus, twelve transdermal patches with new drug modifications have been developed whose adhesive carrier is an acrylate copolymer. The obtained patches were characterized for their adhesive properties and tested for permeability of the active substance. Our results show that the obtained ibuprofen patches demonstrate similar permeability to commercial patches compared to those with structural modifications of ibuprofen. However, these modified patches show an increased drug permeability of 2.3 to even 6.4 times greater than unmodified ibuprofen. Increasing the permeability of the active substance and properties such as adhesion, cohesion, and tack make the obtained patches an excellent alternative to commercial patches containing ibuprofen.

Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.

Seed germination is a complex process enabling plant reproduction. Germination was found to be regulated at the proteome, metabolome and hormonal levels as well as via discrete post-translational modification of proteins including phosphorylation and carbonylation. Redox balance is also involved but less studied. Acer seeds displaying orthodox and recalcitrant characteristics were investigated to determine the levels of redox couples of nicotinamide adenine dinucleotide (NAD) phosphate (NADP) and integrated with the levels of ascorbate and glutathione. NAD and NADP concentrations were higher in Norway maple seeds and exceptionally high at the germinated stage, being the most contrasting parameter between germinating Acer seeds. In contrast, NAD(P)H/NAD(P)+ ratios were higher in sycamore seeds, thus exhibiting higher reducing power. Despite distinct concentrations of ascorbate and glutathione, both seed types attained in embryonic axes and cotyledons had similar ratios of reduced/oxidized forms of ascorbate and half-cell reduction potential of glutathione at the germinated stage. Both species accomplished germination displaying different strategies to modulate redox status. Sycamore produced higher amounts of ascorbate and maintained pyridine nucleotides in reduced forms. Interestingly, lower NAD(P) concentrations limited the regeneration of ascorbate and glutathione but dynamically drove metabolic reactions, particularly in this species, and contributed to faster germination. We suggest that NAD(P) is an important player in regulating redox status during germination in a distinct manner in Norway maple and sycamore seeds.

Modifications of (RS)-2-[4-(2-methylpropyl)phenyl] propanoic acid with amino acid isopropyl esters were synthesised using different methods via a common intermediate. The main reaction was the esterification of the carboxyl group of amino acids with isopropanol and chlorination of the amino group of the amino acid, followed by an exchange or neutralisation reaction and protonation. All of the proposed methods were very efficient, and the compounds obtained have great potential to be more effective drugs with increased skin permeability compared with ibuprofen. In addition, it was shown how the introduction of a modification in the form of an ion pair affects the properties of the obtained compound.

The levels of methionine sulfoxide (MetO) and the abundances of methionine sulfoxide reductases (Msrs) were reported as important for the desiccation tolerance of Acer seeds. To determine whether the MetO/Msrs system is related to reactive oxygen species (ROS) and involved in the regulation of germination in orthodox and recalcitrant seeds, Norway maple and sycamore were investigated. Changes in water content, MetO content, the abundance of MsrB1 and MsrB2 in relation to ROS content and the activity of reductases depending on nicotinamide adenine dinucleotides were monitored. Acer seeds differed in germination speed—substantially higher in sycamore—hydration dynamics, levels of hydrogen peroxide, superoxide anion radicals (O2•−) and hydroxyl radicals (•OH), which exhibited peaks at different stages of germination. The MetO level dynamically changed, particularly in sycamore embryonic axes, where it was positively correlated with the levels of O2•− and the abundance of MsrB1 and negatively with the levels of •OH and the abundance of MsrB2. The MsrB2 abundance increased upon sycamore germination; in contrast, it markedly decreased in Norway maple. We propose that the ROS–MetO–Msr redox system, allowing balanced Met redox homeostasis, participates in the germination process in sycamore, which is characterized by a much higher speed compared to Norway maple.

Two related tree species, Norway maple (Acer platanoides L.) and sycamore (Acer pseudoplatanus L.), produce desiccation-tolerant (orthodox) and desiccation-sensitive (recalcitrant) seeds, respectively. We compared the seeds of these two species to characterize the developmentally driven changes in the levels of peptide-bound methionine sulfoxide (MetO) and the abundance of methionine sulfoxide reductases (Msrs) B1 and B2, with respect to the cellular redox environment. Protein oxidation at the Met level was dynamic only in Norway maple seeds, and the reduced MsrB2 form was detected only in this species. Cell redox status, characterized by the levels of reduced and oxidized ascorbate, glutathione, and nicotinamide adenine dinucleotide (NAD)/phosphate (NADP), was clearly more reduced in the Norway maple seeds than in the sycamore seeds. Clear correlations between MetO levels, changes in water content and redox status were reported in orthodox Acer seeds. The abundance of Msrs was correlated in both species with redox determinants, mainly ascorbate and glutathione. Our data suggest that MsrB2 is associated with the acquisition of desiccation tolerance and that ascorbate might be involved in the redox pathway enabling the regeneration of Msr via intermediates that are not known yet.

Norway maple and sycamore produce desiccation-tolerant (orthodox) and desiccation-sensitive (recalcitrant) seeds, respectively. Drying affects reduction and oxidation (redox) status in seeds. Oxidation of methionine to methionine sulfoxide (MetO) and reduction via methionine sulfoxide reductases (Msrs) have never been investigated in relation to seed desiccation tolerance. MetO levels and the abundance of Msrs were investigated in relation to levels of reactive oxygen species (ROS) such as hydrogen peroxide, superoxide anion radical and hydroxyl radical (•OH), and the levels of ascorbate and glutathione redox couples in gradually dried seeds. Peptide-bound MetO levels were positively correlated with ROS concentrations in the orthodox seeds. In particular, •OH affected MetO levels as well as the abundance of MsrB2 solely in the embryonic axes of Norway maple seeds. In this species, MsrB2 was present in oxidized and reduced forms, and the latter was favored by reduced glutathione and ascorbic acid. In contrast, sycamore seeds accumulated higher ROS levels. Additionally, MsrB2 was oxidized in sycamore throughout dehydration. In this context, the three elements •OH level, MetO content and MsrB2 abundance, linked together uniquely to Norway maple seeds, might be considered important players of the redox network associated with desiccation tolerance.