Marina Kostić

Background/Objectives: Cinnamon bark essential oil (CEO) possesses antimicrobial, antioxidant, and anti-inflammatory properties. However, its topical application is limited by poor aqueous solubility, volatility, and chemical instability. The aim of this study was to develop gelled oil-in-water microemulsions stabilized with Decyl Glucoside for the cutaneous delivery of CEO and to evaluate their physicochemical and pharmaceutical characteristics. Methods: Pseudoternary phase diagrams were constructed to identify the microemulsion regions using Decyl Glucoside, propylene glycol, CEO, isopropyl myristate, and water. Selected CEO-loaded microemulsions were characterized in terms of droplet size, polydispersity index, zeta potential, refractive index, viscosity, and apparent pH, and were subsequently gelled with Aerosil^® 200. The resulting gelled microemulsions were evaluated for CEO content, apparent pH, rheological and textural properties, spreadability, in vitro release and skin permeation studies. The short-term stability of both liquid and gelled microemulsions was also assessed over 45 days. Results: Three CEO-loaded oil-in-water microemulsions were selected from the isotropic regions of the pseudoternary phase diagrams and successfully transformed into homogeneous gelled systems without phase separation. CEO incorporation increased the storage modulus and yield stress of the gelled formulations compared with the corresponding blank systems. The surfactant-to-cosurfactant ratio markedly influenced the rheological properties, mechanical strength, and in vitro release and skin permeation of CEO. Among the investigated formulations, MEG-CEO-2 provided the best balance between mechanical properties, CEO release, and skin permeation. Both liquid and gelled microemulsions maintained their principal physicochemical characteristics during the 45-day stability assessment. Conclusions: Decyl Glucoside-stabilized gelled microemulsions exhibited physicochemical and pharmaceutical properties supporting their further investigation as topical delivery systems for CEO. The results demonstrate that the surfactant-to-cosurfactant ratio can be used to tailor formulation performance, supporting a rational approach for the development of CEO-loaded dermal delivery systems. However, preservation of the biological activities of CEO following incorporation into these systems remains to be experimentally established.

Background: Cydonia oblonga Mill. is a promising plant-derived ingredient for topical formulations due to its phytochemical composition and potential biological and technological properties. This study aimed to evaluate C. oblonga extract as a multifunctional cosmetic ingredient and investigate its concentration-dependent effects on the physicochemical, rheological, and sensory properties of oil-in-water (O/W) emulsions. Materials and Methods: Aqueous and 70% ethanolic extracts were prepared by maceration and reflux extraction and evaluated for phytochemical composition and antioxidant activity. The selected extract was assessed for in vitro biocompatibility and antibacterial activity and incorporated at increasing concentrations (1%, 3%, and 5%) into O/W emulsion creams prepared by a conventional hot emulsification method, involving separate heating of the oil and aqueous phases, followed by their combination under mechanical stirring and subsequent addition of the extract during cooling. The formulations were evaluated for pH, steady-shear, oscillatory and thixotropic rheological properties, and sensory characteristics. Results: Ethanolic reflux extraction yielded the highest total phenolic and flavonoid contents and the strongest DPPH radical-scavenging activity, with chlorogenic acid identified as the predominant phenolic compound. The extract maintained cell viability above 70% in HaCaT keratinocytes and MRC-5 fibroblasts and showed concentration-dependent antibacterial activity. Increasing extract concentration lowered formulation pH and increased structural strength and resistance to deformation, while all formulations retained shear-thinning behavior. Sensory evaluation revealed significant differences in thickness, stickiness, and spreadability. Conclusions: C. oblonga extract demonstrated favorable biocompatibility and multifunctional technological potential for the development of topical semisolid formulations.

Background/Objectives: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease that clinically presents with symptoms of xerostomia and xerophthalmia, as well as a wide range of other symptoms that may affect patients’ daily functioning and life satisfaction. The main purpose of this study was to assess their health-related quality of life (HRQoL) using both general and disease-specific questionnaires. Methods: This cross-sectional observational research with prospective data collection was conducted at the Rheumatology Clinic of the University Clinical Centre of Kragujevac. Participants were divided into two groups: patients with oral manifestations (oral manifestations group) and those presenting with xerostomia only, without other oral lesions or symptoms (xerostomia-only group). A complete clinical examination of the patient’s oral cavity was performed by one doctor of dental medicine. HRQoL was evaluated using various generic and disease-specific instruments. Results: A total of 80 participants were included in the study, of whom 40 were in the oral manifestations group and 40 in the xerostomia-only group. Patients with oral manifestations had significantly higher scores across all PSS-QoL domains compared with the xerostomia-only group (p < 0.001). A statistically significant difference in the total EQ-5D result was detected between groups (0.7 (0.3) vs. 0.8 (0.1), p < 0.001). In multivariable regression analysis (R² = 0.921), the ESSPRI score (β = 0.418, p < 0.001) and the presence of oral manifestations (β = −1.155, p < 0.001) were significant independent predictors of impaired HRQoL, while disease activity showed no significant association (p = 0.895). Conclusions: Patients with primary Sjögren’s syndrome presenting with oral manifestations have poorer HRQoL compared with participants with xerostomia only. Symptom burden, including dryness, pain, fatigue, and oral manifestations, may be associated with decreased HRQoL, in contrast to disease activity.

Background and Objectives: Melanoma is one of the most aggressive malignancies in humans and is associated with an unfavorable prognosis due to its high metastatic potential. In recent decades, increasing incidence and mortality rates have been reported worldwide among Caucasian populations. This study aimed to analyze melanoma incidence and mortality trends in the Republic of Serbia from 2008 to 2022, with a special regard to sex- and age-specific differences. Materials and Methods: A descriptive epidemiological study was conducted using data on all cases of primary cutaneous melanoma (ICD-10 code C43) reported to the Serbian Cancer Registry between 2008 and 2022. Data on newly diagnosed cases and melanoma-related deaths were analyzed by sex and 5-year age groups. Crude rates were calculated per 100,000 populations, whereas age-standardized rates were obtained using direct standardization. Temporal trends were evaluated using the Joinpoint regression analysis. Results: During the study period, 9600 new melanoma cases and 3882 melanoma-related deaths were reported in Serbia. Both incidence and mortality were higher in men (52.5% and 60.1%, respectively). Age-standardized incidence rates remained relatively stable in both sexes, with a slight increase in men (AAPC = 0.9%; 95% CI: −0.5 to 2.3) and a stable trend in women (AAPC = −0.1%; 95% CI: −1.5 to 1.3). Age-standardized mortality rates showed a mild, statistically insignificant decline overall (AAPC = −0.6% in men and −0.9% in women). The calculated mortality-to-incidence ratio (MIR) shows consistently higher values in men compared to women. A significant increase in incidence was observed among men aged 70–74 years (AAPC = 3.1%; p = 0.011), while mortality significantly decreased in women aged 40–44 years (APC = −7.0%; p = 0.017). Conclusions: Melanoma incidence in Serbia remained relatively stable between 2008 and 2022, with a modest increase primarily among older men. Mortality trends showed a slight decline, suggesting potential improvements in early detection and treatment outcomes.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and remains a leading cause of mortality in intensive care units (ICUs). Although the Sequential Organ Failure Assessment (SOFA) score is widely used for prognostic stratification, organ dysfunction represents a downstream manifestation of sepsis, whereas immune and inflammatory dysregulation may precede overt organ failure. Monocyte distribution width (MDW) is a novel hematological parameter reflecting monocyte activation and is approved for the diagnosis of sepsis; however, its prognostic value and potential role within composite biomarker models in critically ill surgical patients with sepsis remain incompletely defined. Methods: We conducted a prospective, observational, single-center pilot study in two surgical intensive care units between November 2022 and December 2023. Adult patients with sepsis defined according to Sepsis-3 criteria were enrolled. Laboratory and clinical variables—including MDW, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), and SOFA score—were measured on admission and during the first five days of ICU stay. Patient-level median values across five days were used for analysis. The primary outcome was in-hospital mortality. Prognostic performance was assessed using receiver operating characteristic (ROC) curve analysis and logistic regression. A composite bioscore was constructed by combining dichotomized MDW, NLR, CRP, and PCT values. Results: Sixty patients were included; 24 (40%) died during hospitalization. Non-survivors were older and had significantly higher SOFA scores. MDW, NLR, CRP, and PCT were significantly higher in non-survivors. SOFA demonstrated the strongest discriminative ability for mortality prediction (AUC 0.839, 95% CI 0.730–0.948). Among biomarkers, NLR (AUC 0.741) and PCT (AUC 0.714) showed good discriminative performance, while MDW (AUC 0.690) and CRP (AUC 0.662) showed moderate discrimination; MDW exhibited the highest specificity (80.6%). In multivariable analysis with individual biomarkers, only SOFA remained an independent predictor of mortality. The composite bioscore demonstrated good discriminative ability (AUC 0.805) and, when evaluated alongside SOFA, remained independently associated with fatal outcome (OR 11.92, 95% CI 1.76–80.75); however, given the modest sample size and wide confidence intervals, this finding should be interpreted with caution. Repeated-measures correlation analysis revealed no strong collinearity among biomarkers. Conclusions: A composite bioscore incorporating MDW, NLR, CRP, and PCT provides prognostic information comparable to SOFA and remains independently associated with mortality. This approach may complement organ dysfunction-based assessment and support early risk stratification in sepsis.

Recent advances in enone chemistry have enabled the development of structurally optimized derivatives with improved anticancer selectivity. In this study, the cytotoxic activity and underlying mechanisms of sodium salts of four α,β-unsaturated enones (ES1–ES4), synthesized from vanillin-based scaffolds, were evaluated in human colorectal carcinoma (HCT-116), cervical adenocarcinoma (HeLa), and normal lung fibroblast (MRC-5) cell lines. All compounds exhibited concentration- and time-dependent cytotoxicity, with ES2 showing the highest potency (IC₅₀ = 14.25 μM in HCT-116 and 18.12 μM in HeLa at 72 h) and minimal toxicity toward MRC-5 cells (IC₅₀ > 90 μM). Although cisplatin demonstrated greater overall cytotoxicity, the enone salts displayed significantly higher selectivity indices, indicating a more favorable therapeutic window. Phase-contrast microscopy revealed characteristic morphological features of apoptosis, including cell rounding and membrane blebbing. Mechanistic investigations confirmed mitochondrial-mediated apoptosis, evidenced by increased early and late apoptotic populations, Bax upregulation, Bcl-2 downregulation, and caspase-3 activation. JC-10 staining demonstrated mitochondrial membrane depolarization accompanied by cytochrome c release. In addition, cell cycle analysis revealed pronounced G2/M phase arrest, particularly in HCT-116 cells. Collectively, these findings indicate that vanillin-derived enone sodium salts exert selective anticancer effects through mitochondrial apoptosis and cell cycle disruption, supporting their potential as low-toxicity anticancer candidates.

Objectives: To analyze the structure of direct treatment costs for FUO and identify key cost-driving factors. Methods: A retrospective pharmacoeconomic analysis using a bottom-up approach was conducted on 71 patients treated for FUO at the Clinic for Infectious Diseases, University Clinical Centre Kragujevac, between 2016 and 2022. Treatment cost data were extracted from the electronic medical records. Results: The total direct cost was €81,655.20, with a mean of €1,150.07 ± 3,434.60 per patient with a median of €549.55 (IQR=€512.62). Major cost components included pharmacotherapy (49.40 %; €40,337.26), diagnostic procedures (30.52 %; €24,923.44), and hospitalisation (10.32 %; €8,324.00). Significant cost determinants were the following: gender, the Charlson comorbidity index, hospital stay duration, number of medications administered per patient, and number of specialist consultations. Conclusions: Pharmacotherapy, especially broad-spectrum antibiotics and antifungals, along with diagnostics and hospitalisation, are the main contributors to FUO treatment costs. Patient-specific factors, particularly comorbidities and service utilisation, play a significant role in determining overall healthcare expenditure.

Background/Objectives: Understanding how plant-derived extracts influence the rheological and sensory behavior of emulsions is crucial for developing stable and consumer-appealing formulations. Although walnut leaf extract (Juglans regia L.) is recognized for its bioactive properties, its structural impact on cosmetic emulsions has not been systematically characterized. This study aimed to investigate the effect of increasing walnut leaf extract concentration on the rheological profile, mechanical integrity during application, and sensory performance of oil-in-water creams. Methods: Four emulsion formulations (F1–F4) containing 0%, 1%, 3%, and 5% walnut leaf extract were prepared using Olivem 1000 and Olivem 300 as emulsifiers. Rheological measurements included amplitude sweep, flow curve, frequency sweep, and thixotropy tests to assess viscoelasticity, flow behavior, and recovery. A sensory evaluation was conducted by trained panelists to correlate rheological parameters with perceived product attributes. Results: All formulations exhibited pseudoplastic, shear-thinning behavior in well-structured cosmetic emulsions during application. The addition of walnut extract significantly modified rheological responses: at 1% concentration, an increase in storage modulus (G′) and shear-thinning ratio (η₀/η∞) indicated structural reinforcement and improved spreadability, whereas higher concentrations (3–5%) led to structural softening and faster thixotropic recovery. The frequency sweep revealed a concentration-dependent shift from elastic- to viscous-dominant behavior. Sensory analysis confirmed these trends, with higher extract levels reducing stickiness and greasiness while enhancing absorption. Conclusions: Walnut leaf extract shows a concentration-dependent influence on the rheological behavior of the emulsions, strengthening the network structure at low levels while promoting softening and faster structural recovery at higher concentrations. The strong correlation between rheological and sensory parameters underscores the potential of walnut extract as a multifunctional ingredient for designing well-structured, non-greasy, and consumer-preferred cosmetic creams.

Background/Objectives: Amlodipine, a widely prescribed calcium channel blocker, has been associated with gingival enlargement, yet the mechanisms underlying this adverse effect remain unclear. The present study aimed to explore molecular and histopathological factors potentially contributing to gingival changes in patients receiving amlodipine therapy, with a particular focus on molecules implicated in extracellular matrix turnover and tissue remodeling. Methods: The study included three groups of participants: patients with amlodipine-induced gingival enlargement, patients with gingival enlargement of inflammatory origin, and amlodipine-treated patients without gingival overgrowth. Gingival tissue samples were analyzed using hematoxylin-eosin staining to assess inflammatory changes and general tissue architecture, and Picrosirius Red staining to visualize collagen fibers. Relative gene expression of alpha-smooth muscle actin (α-SMA), IL-13, MMP-1, and procollagen was determined by real-time PCR, while collagen content was quantified using ImageJ software. Results: Histopathological evaluation revealed a less pronounced inflammatory response in amlodipine-related gingival enlargement compared to those who did not use amlodipine. The highest expression of α-SMA was detected in patients who did not receive amlodipine, whereas IL-13 and procollagen expression were markedly elevated in the amlodipine-induced group compared to others. MMP-1 expression was significantly lower in amlodipine-treated patients relative to those who did not use amlodipine, suggesting impaired collagen degradation. These findings, together with our previous results indicating enhanced expression of profibrotic mediators, suggest that altered extracellular matrix metabolism is potentially dominant in this condition. Conclusions: Amlodipine-induced gingival enlargement appears to involve a multifactorial process characterized by a prominent fibrotic component, reduced matrix degradation, and secondary inflammation.

Background/Objectives: Basil essential oil exhibits a wide range of biological activities, including strong antimicrobial and anti-inflammatory effects. Considering the health benefits of basil essential oil (BEO) and the favorable properties of alkyl polyglucoside emulsifiers, novel Montanov™-68-based O/W creams containing BEO were developed and characterized. Additionally, the influence of the emulsifier content on the cream’s properties was evaluated. Methods: The physicochemical properties were evaluated by organoleptic examination, physical stability test, and pH and electrical conductivity measurement. The mechanical properties were investigated by rheological, textural, and consistency analyses. In addition, a sensory evaluation protocol was applied. Results: The cream formulations containing 5% and 7% Montanov™ 68 demonstrated physical stability, with no evidence of phase separation during the observation period or following accelerated aging. The pH values remained within the acceptable range for topical use, and a gradual decrease in electrical conductivity over time was observed. The rheological analyses confirmed the non-Newtonian pseudoplastic behavior with thixotropic flow characteristics. The textural analyses demonstrated that the higher emulsifier content led to increased firmness, consistency, cohesiveness, and index of viscosity. The sensory analysis revealed differences between the alkyl polyglucoside (APG)-based cream formulations only in terms of the elasticity and stickiness. Conclusions: Although the rheological analyses suggested the better spreadability of the formulation with 5% emulsifier, this was not confirmed by the sensory analysis. However, the APG-based formulations performed significantly better than the synthetic surfactant-based formulation in terms of the absorption, stickiness, and greasiness (during and after application). These results are encouraging for the further evaluation of APG-based creams containing basil essential oil for topical application.