Fumaria officinalis Dust as a Source of Bioactives for Potential Dermal Application: Optimization of Extraction Procedures, Phytochemical Profiling, and Effects Related to Skin Health Benefits

Fumaria officinalis (fumitory), in the form of dust, was employed as a source of bioactive extracts whose chemical profile and biological potential were investigated. According to the results of the optimization of the extraction protocol, the extract with the highest polyphenol yield was prepared using fumitory dust under the optimal conditions determined using the statistical tool, 23 full factorial design: 50% ethanol and a 30:1 mL/g ratio during 120 s of microwave extraction (22.56 mg gallic acid equivalent/g of plant material). LC-MS and spectrophotometric/gravimetric analyses quantified the polyphenol, flavonoid, tannin, alkaloid, and protein contents. Caffeoylmalic acid, quercetin dihexoside, quercetin pentoside hexoside, rutin, and methylquercetin dihexoside were the most dominant compounds. The highest total flavonoid, condensed tannin, alkaloid, and protein yields were determined in the extract prepared using microwaves. In addition to the proven antioxidant potential, in the present study, the anti-inflammatory activity of fumitory extracts is also proven in the keratinocyte model, as well as a significant reduction of H2O2-induced reactive oxygen species production in cells and the absence of keratinocyte cytotoxicity. Thus, detailed chemical profiles and investigated biological effects related to skin health benefits encourage the potential application of fumitory dust extracts in dermo-cosmetic and pharmaceutical preparations for dermatological circumstances

Associations of excessive gestational weight gain with changes in components of maternal reverse cholesterol transport and neonatal outcomes

Excessive gestational weight gain may be associated with unfavorable pregnancy outcomes. We explored the impact of excessive weight gain on components of HDL metabolism in maternal plasma: sterol composition of HDL particles, distribution of HDL subclasses and SCARB1, ABCA1 and ABCG1 genes expressions and their associations with newborns' characteristics. The study included 124 pregnant women, 58 with recommended and 66 with excessive weight gain. Concentrations of cholesterol synthesis marker, desmosterol, within HDL increased during pregnancy in both groups of participants. In women with excessive weight gain, levels of cholesterol absorption marker, campesterol, within HDL were significantly lower in the 3rd trimester compared to the 1st and 2nd trimesters. Relative proportions of large HDL 2b subclasses increased during pregnancy in women with recommended weight gain. Women with high pre-pregnancy BMI and excessive gestational weight gain had the lowest levels of β-sitosterol within HDL and the highest relative proportions of HDL 3a and HDL 3b subclasses in the 2nd trimester. Large HDL 2b particles were in positive correlation, while smaller HDL 3 subclasses and SCARB1 gene expressions were in negative correlation with APGAR scores. In conclusion, excessive weight gain could contribute to altered metabolism of HDL, and subsequently to poorer neonatal outcomes

Strawberry and Drupe Fruit Wines Antioxidant Activity and Protective Effect Against Induced Oxidative Stress in Rat Synaptosomes

The aim of this study was to investigate the antioxidant capacity of fruit wines and their protective effects against hydrogen peroxide-induced oxidative stress in rat synaptosomes in vitro. The wines were produced from strawberries and drupe fruits (i.e., plum, sweet cherry, peach, and apricot) through microvinification with a pure S. cerevisiae yeast culture. Fruit wines were produced with and without added sugar before the start of fermentation, whereas subvariants with and without pits were only applied to drupe fruit wines. First, synaptosomes were treated with the wines, while oxidative stress was induced with H2O2. Subsequently, the activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of malondialdehyde (MDA), an indicator of membrane injury, were determined. In addition, the Briggs–Rauscher reaction (BR) was used to evaluate the inhibition capacity against free radicals. All investigated fruit wines increased the activity of the studied antioxidant enzymes and decreased MDA content compared to the corresponding controls (synaptosomes treated with H2O2). After synaptosomal treatment with plum wine, the highest activities were observed for SOD (5.57 U/mg protein) and GPx (0.015 U/mg protein). Strawberry wine induced the highest CAT activity (0.047 U/mg protein) and showed the best ability to reduce lipid peroxidation, yielding the lowest MDA level (2.68 nmol/mg). Strawberry, plum, and sweet cherry wines were identified as samples with higher antioxidant activity in both principal component analysis (PCA) and hierarchical cluster analysis (HCA). Finally, plum wine exhibited the highest inhibitory activity in the BR reaction (397 s). The results suggest that fruit wines could be considered potential functional food due to their protective effects against oxidative stress

Enzimski i lipidni markeri u proceni rizika za nastanak kardiovaskularnih bolesti kod žena u menopauzi

Postmenopausal women are at an increased risk of cardiovascular disease (CVD), the leading cause of death worldwide, compared with younger women. Gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-c) are linked with oxidative stress, inflammation, insulin resistance, and CVD risk factors. However, there have been no studies that examined the relationship between GGT/HDL-c and CVD exclusively in women who are not of reproductive age. Therefore, we aimed to examine this potential relationship in a cohort of CVD- free postmenopausal women. A total of 150 disease-free postmenopausal women were consecutively included. CVD risk was defined according to high sensitivity C-reactive protein (hsCRP) concentration (hsCRP < 1 mg/L defines low risk and hsCRP ≥ 1 mg/L defines intermediate and high risk). The GGT/HDL-c was independently associated with intermediate and high CVD risk in postmenopausal women. As this enzyme/lipid index increased by 1 unit, the probability of intermediate and high CVD risk rose by 10.3% (OR = 1.103, p = 0.024). The GGT/HDL-c ratio was independently associated with higher CVD risk, as measured with hsCRP in postmenopausal women. This cost-effective, easily measured, and widely available index could be used in everyday clinical practice for estimating CVD risk in postmenopausal women.Žene u postmenopauzi su pod povećanim rizikom od kardiovaskularnih bolesti (KVB), vodećeg uzroka smrti širom sveta, u poređenju sa mlađim ženama. Gama-glutamil transferaza (GGT) i koncentracija holesterola u lipoproteinima visoke gustine (HDL-c) povezani su sa oksidativnim stresom, upalom, insulinskom rezistencijom i faktorima rizika za KVB. Međutim, ne postoje studije koje su ispitivale odnos između GGT/HDL-c i KVB isključivo kod žena koje nisu u reproduktivnom dobu. Stoga smo imali za cilj da ispitamo pomenuti potencijalni odnos u kohorti žena u postmenopauzi bez KVB. Ukupno je uključeno 150 zdravih žena u postmenopauzi. Rizik od KVB je definisan prema koncentraciji visokosenzitivnog C-reaktivnog proteina (hsCRP) (hsCRP < 1 mg/L definiše nizak rizik, a hsCRP ≥ 1 mg/L definiše srednji i visoki rizik). GGT/HDL-c je bio nezavisno povezan sa srednjim i visokim rizikom od KVB kod žena u postmenopauzi. S povećanjem ovog enzimskog/lipidnog indeksa za 1 jedinicu, verovatnoća srednjeg i visokog rizika od KVB porasla je za 10,3% (OR = 1,103, p = 0,024). Odnos GGT/HDL- c je nezavisno povezan sa većim rizikom od KVB, merenim pomoću hsCRP kod žena u postmenopauzi. Ovaj isplativ, lako merljiv i široko dostupan indeks mogao bi se koristiti u svakodnevnoj kliničkoj praksi za procenu rizika od KVB kod žena u postmenopauzi

Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models

Skin acts as a dynamic interface with the environment. Pathological alterations in the skin barrier are associated with skin diseases. These conditions are characterized by specific impairments in epidermal barrier functions. Despite its protective nature, the skin can be a relevant route of drug administration, both for topical and transdermal therapy, allowing for improved drug delivery and reducing the incidence of adverse reactions. This manuscript reviews transcutaneous drug delivery as a strategy for treating localized and systemic conditions, highlighting the importance of skin models in the evaluation of drug efficacy and barrier function. It explores advances in in vitro, ex vivo, in vivo, and in silico models for studying cellular uptake, wound healing, oxidative stress, anti-inflammatory and immune modulation activities. Disease-specific skin models are also discussed

Donut-shaped [NaP5W30O110]14− polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action

The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH4)14[NaP5W30O110] 31H2O (NaP5W30) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20 mg/kg/day NaP5W30 for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP5W30 (20 mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP5W30 significantly reduced hyperglycemia and glycated haemoglobin A1c (HbA1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP5W30 treatment group compared to the diabetic control group. In contrast, NaP5W30 had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP5W30 effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP5W30 did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP5W30 could be considered a promising antidiabetic drug-candidate that deserves further investigation

The second victim experience and support tool: a cross-cultural adaptation, validation and psychometric evaluation of the Serbian version for pharmacy professionals (SR-SVEST-R)

Background: The second victim phenomenon, involving emotional and psychological distress after adverse events, is underexplored among pharmacy professionals. The validated Second Victim Experience and Support Tool measures these experiences and support options, with the improved version also assessing resilience. Aim: This study aimed to validate the Second Victim Experience and Support Tool-Revised, measure the second victim phenomenon, and present results among pharmacy professionals in Serbia. Method: This cross-sectional study included 350 pharmacy professionals (MPharm and technicians). The questionnaire, with 9 factors and 35 statements, was translated and adapted following guidelines, and the content was validated by five experts. A pre-test with 30 participants ensured clarity, followed by Confirmatory Factor Analysis for construct validity and Cronbach's Alpha for reliability. Results: Content validity was confirmed with item scores from 0.8 to 1 and a mean scale score of 0.83. Factor analysis identified 9 factors and 30 items (Chi-square = 545.6, degrees of freedom = 366, p < 0.001). The model fit was supported by a Root Mean Square Error of Approximation of 0.037, a Comparative Fit Index of 0.958, a Tucker-Lewis Index of 0.950, and a Standardised Root Mean Square Residual of 0.040. Reliability analysis showed a Cronbach's alpha of 0.88, with factor values from 0.60 to 0.90. Among participants, 49.5% feared future events, 47.4% felt exhausted, 22.6% considered quitting, 72.6% valued peer support, and 28.9% improved work quality. Conclusion: The Serbian resilience measuring tool is valid and reliable, effectively evaluating second victim experiences and support, with half of pharmacy professionals affected

Assessment of causes of stress in a pharmacy student population during semester and exam period

Stress is one of the most significant factors that can influence the academicperformance of students. To explore the causes of stress in students, the crosssectionalonline survey was conducted during semester (in 2019 year) and duringexamination period (in 2020 year) period at the University of Belgrade - Faculty ofPharmacy. The main results indicated that female gender was the most significantpredictor of stress during the examimation period, and the most frequent stresssources were limited time to prepare exams and/or colloquia. The role of family,friends, and boyfriend/girlfriend showed to be of great importance in stress reductionduring the semester and especially during the examimation period. The most frequentmanifestations of stress were feeling nervous, tired and worried. For stress reductionstudents usually listened to music and talked with friends. Therefore, student’sobligations and their overall living conditions should be observed comprehensively.These results may indicate further actions to decrease stress levels in students, andneed for academic environment that may help students to achieve the best academicperformance.Peer-reviewed manuscript: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/4239

Lignin-Based Nanocarrier for Simultaneous Delivery of 131I and SN-38 in the Combined Treatment of Solid Tumors by a Nanobrachytherapy Approach

Background: The rapid rise in cancer incidence significantly augments efforts to improve cancer treatments. A multimodal approach in the nanobrachytherapy of solid tumors is one of the promising methods under investigation. This study presents a novel biocompatible lignin-based nanomaterial, loaded with cytostatic agent SN-38 and radionuclide 131I, for simultaneous radiation and chemotherapy of solid tumors by a nanobrachytherapy approach. Method: Nanoparticles of ~100 nm in size, composed of lignin alone or loaded with 10% (m/m) of SN-38 (SN-38@lignin), were synthesized using a bottom-up approach and characterized. Subsequent radiolabeling of the nanoparticles by 131I produced 131I-lignin and 131I-SN-38@lignin. Their antitumor efficiency was tested against luciferase-expressing 4T1 mouse breast cancer xenografts of ~100 mm3 size on Balb/c mice. Results: An intratumoral injection of 1.85 MBq of 131I-lignin was retained within the tumor and achieved a moderate twofold decrease in tumor size compared to the control group. Injecting SN-38@lignin containing 25 µg of SN-38 decreased tumor size 3.5-fold. The therapy using the same doses of 131I-SN-38@lignin produced the most potent antitumor effect, with tumors being 6-fold smaller and having extensive intratumoral necrosis, all of it without signs of systemic toxicity. Conclusions: These results support the intratumoral delivery of lignin-based nanomaterial carrying radioisotopes and camptothecins for effective multimodal anticancer therapy