ABSTRACT The pharmaceutical market has recently witnessed the advent of a novel tetrahydrotriazene molecule belonging to the new pharmacological class “Glimins”, named Imeglimin (IMG). It has been approved in Japan as a safe and highly effective oral diabetic drug for type II diabetic patients. It enhances the function of β‐cells in the human pancreas and increases insulin sensitivity. Hence, this work was directed to provide a fast, sensitive and highly reliable bioanalytical method for its quantification in human plasma. What makes this work greatly distinctive is first: adopting an ultra‐performance liquid chromatography (UPLC) with protein precipitation as a fast and straightforward sample preparation protocol with the highest extraction recovery. Secondly, utilisation of the stable isotope‐labelled molecule, IMG‐d6, rather than a structurally similar analogue, to avoid the interference of any co‐administered drugs in human plasma. Samples were extracted with acetonitrile and then chromatographically separated using an Acquity UPLC BEH HILIC column of 1.7 µm particle size along with a mobile phase solution composed of 70:30 (v/v) acetonitrile and 10 mM ammonium formate buffer acidified with 0.1% formic acid. Upon adjusting the flow rate to 0.3 mL/min, IMG was eluted at 1.3 min with a total run time of only 2.0 min. Mass quantification was performed in positive electrospray ionisation operated in multiple reaction monitoring mode. IMG was quantified at m/z of 156.05 → 112.91 transition pairs while IMG‐d6, at m/z 162.11 → 119.04. The proposed UPLC‐tandem mass spectrometry method was thoroughly validated as per Food and Drug Administration principles over a linearity range of 10.0–3000.0 ng/mL and successfully applied for IMG quantification in human plasma samples. The scope of the work was extended to encompass real analysis of collected human blood samples, calculation of IMG pharmacokinetics parameters and conductance of a bioequivalence study between the IMG generic product versus brand one.
Obesity includes a wide range of metabolic conditions. Some patients remain metabolically healthy despite excess body weight (MHO phenotype), while others develop metabolic syndrome and metabolic dysfunction–associated fatty liver disease (MAFLD). These differences may determine the risk of diabetes and cardiovascular disease. The present study compared clinical and biochemical characteristics between people with MHO and those with MetS combined with MAFLD, and evaluated the effects of six months of metformin therapy in the latter group. A total of 78 adults with obesity (BMI ≥ 30 kg/m2) were examined. Participants were classified as MHO (n = 26) or as having metabolic syndrome with MAFLD (n = 52). Anthropometric data, glucose and lipid metabolism indicators, liver enzymes, and non-invasive measures of hepatic steatosis and fibrosis (CAP, FIB-4, HSI) were recorded. Patients with MetS + MAFLD were randomized to lifestyle modification (Mediterranean diet and moderate exercise) or the same program plus metformin (500 mg twice daily) for six months. After six months, patients in the metformin group showed significant improvements in fasting glucose (− 0.9 ± 0.4 mmol/L, p < 0.001), HbA1c (− 0.5 ± 0.2
ABSTRACT Curcumin is a natural polyphenol derived from Curcuma longa with well‐documented anti‐inflammatory, antioxidant, antimicrobial, and wound‐healing properties. However, its clinical application in dermatology remains limited due to its low water solubility, low stability, and limited skin penetration. Recent advances in nanotechnology have enabled the development of curcumin delivery systems designed to improve dermal bioavailability, stability, and controlled release. Our novelty lies in integrating bibliometric analyses with a translational emphasis on food‐grade nanocarriers. This review highlights the therapeutic relevance of curcumin in major skin conditions, such as psoriasis, atopic dermatitis, acne, wound healing, burns, and skin cancer, with an emphasis on lipid‐ and polymer‐based nanoformulations, such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, and hydrogel‐based platforms. Furthermore, the bibliometric analysis highlights a growing scientific interest in curcumin nanotherapies, although clinical evidence remains limited. In general, curcumin nanoformulations represent promising strategies for topical dermatological applications, but further clinical validation and regulatory development are required to support their application in therapeutic products.
Aim - to assess dietary folate intake, serum folate levels, and their associations with disease characteristics in children with juvenile idiopathic arthritis (JIA). Materials and methods. A prospective cohort study was conducted including children with JIA and healthy controls. Dietary folate intake was assessed using a food frequency questionnaire. Serum folate concentrations were measured by enzyme-linked immunosorbent assay. Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score (JADAS-27). Results. Insufficient dietary folate intake was observed in most JIA children (96.46%) and healthy controls (87.88%), with significantly lower median daily folate intake in JIA group. In contrast, JIA children had significantly higher serum folate concentrations and a lower prevalence of folate deficiency or possible deficiency than healthy controls (14.58% vs. 51.61%, respectively). This finding is likely explained by routine folic acid supplementation in patients receiving methotrexate therapy. No significant associations were found between serum folate concentrations and JIA disease activity, disease duration, or disease subtype. Folate deficiency or possible deficiency in children with JIA was associated with rural residence. Conclusions. Despite inadequate dietary folate intake, children with JIA had higher serum folate concentrations than healthy peers, most likely due to folic acid supplementation during methotrexate treatment. The high prevalence of folate deficiency in the general pediatric population highlights the importance of addressing micronutrient insufficiency. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.
Treatment of newborns in neonatal intensive care units (NICUs) is associated with exposure to multifactorial stressors, which adversely affect the physical and psychological status of infants as well as the psycho-emotional state of their mothers. In this context, the use of non-invasive assessment of stress biomarkers has gained increasing importance. Aim. To evaluate neonatal and maternal stress in the NICU by measuring indicators of sympathoadrenal and serotonergic system function and to analyze stress-inducing factors. Materials and Methods. The study included 117 newborns admitted to the NICU of the regional perinatal center. The infants were divided into three groups according to gestational age at birth: Group 1 – extremely and very preterm infants (EVPI), <32 weeks, n = 35; Group 2 – moderate and late preterm infants (MLPI), ≥32 weeks, n = 61; Group 3 – term newborns, n = 21. The following stress biomarkers were measured: 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite and functional marker of the serotonergic system; and salivary alpha-amylase (sAA), a biomarker of the sympathoadrenal system activity reflecting the sympathetic division of the autonomic nervous system response to stress. Written informed consent was obtained from the parents of all participants. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Bioethics Committee of I. Ya. Horbachevsky Ternopil National Medical University, Ministry of Health of Ukraine (Protocol No. 73, April 3, 2023). Statistical analysis was conducted using STATISTICA 13.0 software (StatSoft Inc., Tulsa, OK, USA). Medians (Me), upper quartiles (Uq), and lower quartiles (Lq) were calculated. For comparison of numerical variables with non-normal distribution, the Mann-Whitney U test (for two independent groups), the Kruskal–Wallis test (for three independent groups), and the Wilcoxon signed-rank test (for two dependent groups) were applied. Statistical significance was set at p < 0.05. The research project was entitled “Assessment of neonatal and parental stress in the neonatal intensive care unit and methods of its correction”, State registration No. 0123U100063, the study period was December 2022 – November 2025. Results. In extremely preterm infants, urinary 5-HIAA levels increased after skin-to-skin contact (SSC) from 2.064 [1.423; 3.402] to 4.366 [2.592; 9.468] mg/L (p = 0.008). In the moderate and late preterm group, levels increased from 2.247 [1.530; 3.217] to 5.001 [2.812; 9.567] mg/L (p < 0.001). In term infants, 5-HIAA levels increased from 2.452 [1.861; 5.587] to 4.293 [3.565; 8.420] mg/L; however, this change was not statistically significant (p = 0.075). Decreased 5-HIAA levels in preterm infants were associated with low Apgar scores (<7 points), need for resuscitation, surfactant administration, mechanical ventilation, intraventricular hemorrhage, necrotizing enterocolitis, patent ductus arteriosus, anemia, and neonatal jaundice requiring phototherapy. In infants <32 weeks’ gestation, sAA levels after SSC decreased from 52.74 [38.54; 107.10] to 19.65 [15.15; 26.98] U/mL (p = 0.001). In infants ≥32 weeks, sAA levels decreased from 71.49 [34.98; 106.46] to 23.51 [17.39; 34.36] U/mL (p < 0.001). In term infants, sAA levels decreased from 84.24 [61.25; 101.03] to 31.37 [25.62; 42.78] U/mL (p < 0.005). Maternal sAA levels decreased correspondingly: in mothers of extremely and very preterm infants from 88.85 [51.66; 109.90] to 34.13 [23.59; 57.45] U/mL (p = 0.033); in mothers of moderate and late preterm infants from 68.85 [42.30; 98.64] to 25.03 [17.30; 29.59] U/mL (p < 0.001); and in mothers of term infants from 79.34 [54.21; 92.77] to 38.29 [22.88; 47.50] U/mL (p < 0.005). Breastfeeding in the NICU was associated with additional reduction in maternal stress: maternal sAA levels before SSC were 49.20 [28.19; 75.64] U/mL in breastfeeding mothers compared with 105.90 [80.41; 148.10] U/mL in mothers who formula-fed their infants (p = 0.046). Conclusions. Skin-to-skin contact and rooming-in in the NICU are evidence-based interventions that effectively reduce stress in both mothers and newborns, as indicated by changes in markers of serotonergic and sympathoadrenal system activity, whereas neonatal morbidity is associated with increased stress levels. Breastfeeding of preterm infants in the NICU is associated with a significant reduction in maternal stress.
