The high cost of modern wound dressings remains a burden for low-income patients. Formulating honey, gotu kola extract, and kappa-carrageenan into a hydrogel film represents a promising, cost-effective alternative, given their sustainability, low cost, and natural abundance. The study aimed to determine the optimal formula for a honey/gotu kola/kappa-carrageenan-based hydro-gel film and to evaluate its wound-healing activity in a rat excision wound model, along with histopathology and immunohistochemistry. In this study, eight formulations of kappa-carrageenan hydrogel were designed using a simple casting method with various honey concentrations (10-40%) and different plasticizers, namely sorbitol and glycerol. The formula with the lowest honey content and sorbitol as a plasticizer yielded the most transparent, thinnest film with the highest swelling capacity. Adding 0.5% w/w gotu kola extract still maintained its mechanical characteristics, high swelling capacity, and a preferable active content release profile. It significantly accelerated wound healing by creating unfavorable conditions for bacterial growth, inducing extracellular matrix and collagen type I depositions, and enhancing angiogenesis.
Pharyngeal cancer is one of the most aggressive malignancies, often diagnosed at advanced stages, with current therapeutic options facing significant limitations in terms of efficacy and tolerability. Therefore, natural compounds, often characterized by a more favorable safety profile, could represent a promising option in the therapeutic management of this disease. In this context, the present study evaluated the cytotoxic potential of two flavonoids, fisetin (FIS) and genistein (GEN), and their combination on a 2D pharyngeal cancer cell model, Detroit-562. The study included an analysis of cell viability using the MTT assay and LDH release, followed by assessment of cell morphology and essential organelles, such as the nuclei and mitochondria, and evaluation of pro-apoptotic and necrotic effects via AO/PI double staining. In addition, the combination's irritant potential was analyzed in the HET-CAM in ovo model. The results showed that, across all assays, the combinatorial treatment exhibited higher cytotoxicity without causing an irritant effect on the vascular plexus, supporting its potential use as an adjuvant therapy for the treatment of pharyngeal cancer.
This study evaluated the effects of prolonged exposure to environmentally relevant levels of glyphosate, administered alone or in combination with dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D), on behavioral outcomes and brain integrity in a rat model. Exposure was initiated during gestation and continued through postnatal development until early adulthood. Animals subjected to herbicide exposure exhibited alterations in locomotor activity, anxiety-related behavior, stress responses, and motor coordination, with more pronounced effects observed following combined exposure. These functional changes were associated with histopathological evidence of neuronal degeneration and vascular alterations, alongside biochemical indicators of oxidative imbalance in brain tissue. Our findings indicate that chronic exposure to low-dose herbicides during critical neurodevelopmental windows may induce persistent neurobehavioral and structural brain changes. The enhanced effects observed under mixture exposure conditions highlight the importance of considering combined environmental exposures in toxicological risk assessment.
Post-stroke rehabilitation patients require complex pharmacotherapy, increasing their risk of potential drug-drug interactions (pDDIs). The study aimed to assess the prevalence, types, and predictors of clinically relevant pDDIs in post-stroke patients during rehabilitation. This prospective observational study was conducted at the Institute for Physical Medicine, Rehabilitation, and Orthopaedic Surgery. Clinically relevant pDDIs were identified using Lexi-Drugs. The study included 217 post-stroke rehabilitation patients (86.2% ischaemic stroke). At least one clinically relevant pDDI was present in 96.3% of ischaemic and 76.7% of haemorrhagic stroke patients (p < 0.001). Ischaemic stroke history was an independent predictor for higher pDDI risk (OR 5.3; p < 0.05). The study revealed a high prevalence of potentially clinically relevant pDDIs in post-stroke rehabilitation patients, particularly among those with ischaemic stroke. Additionally, comorbidities such as pneumonia or constipation increased the risk of pDDIs occurrence. Given the complexity of post-stroke pharmacotherapy, systematic screening and management strategies are crucial to minimise the risk of preventable adverse drug interactions and improve rehabilitation outcomes.
Captopril, a BCS Class I drug, is widely used in the treatment of hypertension but faces challenges such as dose dumping and degradation in the intestinal environment. The present study aimed to develop 3D-printed floating capsules for both immediate and sustained release of captopril to improve gastric retention and reduce dosing frequency. Using fused deposition modeling, two designs, a dome-shaped and a multicompartment FC, were fabricated and evaluated for weight, dimensions, buoyancy under dynamic conditions, structural integrity, and drug release at pH 1.2. Both devices remained intact with no leakage. The dome-shaped FC showed a floating time of 5 h, while the multicompartment FC floated for 24 h. In vitro release studies demonstrated that the dome-shaped, Multicompartment FC released the drug at 390 or 480 min, compared with conventional gelatin capsules, which released the drug within 25 min. Thus, the 3D-printed systems exhibited gastroretentive and controlled-release properties. In conclusion, 3D-printed FCs enabled both immediate and sustained captopril release, with release performance influenced by wall thickness and compartmental design, highlighting their potential as advanced gastroretentive drug delivery systems.
This retrospective study compared the efficacy and safety of low molecular weight heparin (LMWH) combined with rivaroxaban versus LMWH plus warfarin in elderly patients with acute pulmonary embolism (PE). A total of 159 patients aged > 60 years with intermediate-low risk acute PE were included: 79 received LMWH plus warfarin and 80 received LMWH plus rivaroxaban. Clinical efficacy, coagulation parameters, biochemical markers, cardiopulmonary function, CTPA findings, and adverse events were evaluated up to 6 months after treatment. The total effective rate was significantly higher in the rivaroxaban group than in the warfarin group (86.25% vs. 69.62%, p = 0.042). Patients treated with rivaroxaban showed better coagulation profiles, including longer PT and lower D-dimer levels, improved oxygenation (PaO2), and a higher thrombus lysis rate (all p < 0.05). In addition, bleeding events and the need for INR monitoring were significantly reduced in the rivaroxaban group. No significant differences were observed in gastrointestinal reactions or re-embolism rates. LMWH combined with rivaroxaban demonstrated superior efficacy and safety compared with the conventional warfarin regimen and may represent a preferable anticoagulation strategy in elderly patients with acute PE.
Osteoarthritis (OA) is the most prevalent form of arthritis, affecting millions globally. Polynucleotides (PN)-based intra-articular injections have demonstrated efficacy as therapeutic agents for OA management. This study investigated the durability of the therapeutic efficacy of polynucleotide-chitosan formulation (PCF) with that of a conventional PN formulation (PNF) in a monoiodoacetate (MIA)-induced rat model of OA. In addition, the effect of the PCF on cartilage integrity was assessed through histological staining and modified scoring systems for cartilage destruction and inflammation. In the weight-bearing test, the PCF exhibited a longer attenuation duration than the PNF. Histological analyses indicated that the PCF reduced surface irregularities and cartilage destruction. These findings suggest that the PCF may represent a promising therapeutic option for OA.
Drug shortages represent a challenge for healthcare systems, particularly affecting essential medicines. This study investigates the relationship between long-term price dynamics and supply disruptions within the ATC J01 class in Romania. A retrospective observational analysis was conducted using wholesale price data (2008-2024) and official shortage notifications (2017-2025). Price erosion indicators were calculated, and their association with supply disruptions was assessed using comparative statistics and logistic regression. Results showed that antibiotics associated with shortages experienced significantly lower overall price erosion over the 2008-2024 period than those without disruptions (p < 0.01). Logistic regression confirmed an inverse association between price erosion and the probability of shortage (OR = 0.758). These findings suggest that market rigidity, rather than price compression alone, may represent a key determinant of supply vulnerability. Greater price flexibility may reflect competitive and adaptive market conditions that enhance supply resilience. The study highlights the need for balanced pharmaceutical policies integrating affordability with long-term market sustainability.
This study investigates the phytochemical composition, antioxidant activity, and cytoprotective potential of Ulva lactuca hydroethanolic extracts. The extract was subjected to standard phytochemical screening, confirming the presence of bioactive compounds including polyphenols, flavonoids, tannins, and terpenoids. Quantitative analysis indicated high levels of carbohydrates and proteins, with strong antioxidant potential (IC50 = 0.26 mg/mL). Experimental type 2 diabetes was induced in adult rats through a high-fat diet (HFD) followed by a single intraperitoneal injection of streptozotocin (35 mg/kg). Oxidative stress markers (lipid peroxidation, hydroperoxides, protein carbonyls), antioxidant enzyme activities, paraoxonase-1 (PON1), and non-enzymatic antioxidants were assessed in serum, red blood cells, lipoproteins, and tissues. Treatment with either whole algae or its extract significantly reduced oxidative stress markers and restored antioxidant enzyme activities, thiol content, and levels of vitamins C and E. Notably, the extract showed greater efficacy in kidneys and red blood cells, while whole algae enhanced PON1 activity and preserved vitamin status. These findings demonstrate the potent antioxidant and protective effects of U. lactuca and support its potential role in mitigating oxidative damage and complications associated with type 2 diabetes.
This study aims to examine the concomitant use of indapamide and allopurinol in 1840 electronic health records (EHRs) from the health insurance system for patients aged 30 to 100 with chronic conditions as of January 2024. 509/1840 EHRs had indapamide, and 72/1840 had allopurinol; of the 72 EHRs with allopurinol, 31 contained it associated with indapamide. The recommendation for allopurinol is strongly associated with indapamide use (p = 0.004) and with indapamide dose (p = 0.018), particularly with 1.5 mg (p = 0.003). Indapamide prescriptions are significantly associated with gender, age group, and allopurinol dose (p < 0.05). There was a significant association between gender and the daily allopurinol dose (chi(2), p = 0.006). The present findings highlight the need to establish the true frequency of hyperuricemia with indapamide (currently listed as unknown in the current SmPCs), which is determined, on the one hand, by the large number of patients treated and, on the other hand, by the long-term consequences (renal damage and gout).
Clinical toxicology laboratories require robust and sensitive analytical methods to address the increasing prevalence of new psychoactive substances (NPS). This study developed and validated two complementary analytical methods, gas chromatography-tandem mass spectrometry (GC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the quantitative analysis of six key NPS in human urine, including alpha-pyrrolidinovalerophenone (alpha-PVP), 4-methylethcathinone (4-MEC), 3',4'- methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-alpha-pyrrolidinobutiophenone (MDPB), N-(2-Methoxybenzyl)-4-iodo-2,5-dimethoxyphenethylamine (25-NBOMe) and 4-fluoromethcathinone (4-FMC). Both methods were validated according to established guidelines, assessing parameters such as linearity, sensitivity, precision, and accuracy. Both GC-MS/MS and LC-MS/MS methods demonstrated excellent linearity with coefficients of determination (R-2) above 0.99. However, the LC-MS/MS method proved to be significantly more sensitive and accurate. It achieved a limit of quantification (LOQ) of 1 & micro;g/L, a substantial improvement over the 200 & micro;g/L LOQ of the GC-MS/MS method. Despite the quantitative limitations imposed by higher bias, the GC-MS/MS framework maintains its procedural significance, serving as a vital tool for the confirmatory identification of these emerging NPS. These parallel analytical trajectories act as complementary frameworks, delivering an empirical evaluation of their deployment in clinical practice for thorough toxicological surveillance.
Pancreatic ductal adenocarcinoma (PDAC) is a global public health issue and ranks among the top causes of death. Statistically, it is the third leading cause of cancer-related deaths in developed countries, including Europe. Given the current unsatisfactory treatment options, the concept of drug repurposing (the use of approved drugs for other purposes) represents an alternative approach of interest in pancreatic cancer. For this reason, this research proposes to explore the potential effects of digoxin and digitoxin, two digitalis compounds, on cytotoxicity, pro-apoptosis and antiproliferation in MIA PaCa-2 pancreatic cancer cells, in light of the limited and inconclusive results regarding the ability of these drugs in pancreatic cancer therapy. Towards this purpose, DGX and DGTX were evaluated on the cells using several types of preclinical experiments (MTT assay, bright-field morphological analysis, nuclear assessment through Hoechst 33342, mitochondrial via MitoTracker, acridine orange/propidium iodide analysis regarding the occurrence of apoptosis and necrosis and colony formation assay), as well as in ovo assessment of each agent's irritant capacity on the chorioallantoic membrane using the HET-CAM method.
The design of new anticancer agents aims to develop powerful treatments with fewer side effects. Using the Genetic Optimization for Ligand Docking (GOLD) software, new naproxen-based compounds were designed and primarily screened for anticancer efficacy by interacting with the estrogen receptor, Protein Data Bank (PDB) code: 3ERT. The new derivatives can be synthesized by reacting naproxen with semicarbazide to form the intermediate (N) and then reacting the N with an aldehyde (Schiff base reaction) to produce the final compounds (N1A-N9A). To anticipate the pharmacokinetics of the designed compounds, computational approaches, including absorption, distribution, metabolism, and excretion (ADME) studies, were performed using the Swiss ADME server. In addition, all of the designed compounds met the rule of five for M.W., H-bond acceptor, and topological polar surface area (TPSA), but did not meet the H-bond donor and partition coefficient. Compounds (N9A, N4A) interacting with amino acids in the active pocket of docking studies of ligands with the ER-alpha protein (breast cancer protein) showed increased Piecewise Linear Potential (PLP) fitness values near the reference tamoxifen, suggesting potential activity. Throughout the simulation period, the molecule S2 exhibited stable fluctuations, with root-mean-square deviation (RMSD) values below 3 & Aring; when modeled in the enzyme pocket.
This retrospective study evaluated the effects of denosumab combined with calcitriol on bone metabolism, vertebral recovery, and refracture risk in elderly patients with osteoporotic vertebral compression fractures (OVCF) after percutaneous kyphoplasty (PKP). A total of 152 patients were divided into a control group (calcitriol, n = 76) and an observation group (denosumab plus calcitriol, n = 76) for 12 months. Radiological parameters and bone metabolism markers were assessed preoperatively and up to 12 months postoperatively. The observation group showed significantly improved vertebral anterior height recovery (82.3 +/- 6.1% vs. 73.5 +/- 7.8%), better Cobb angle correction, and a lower cement leakage rate (7.89% vs. 14.47%). At 6 and 12 months, bone mineral density and formation markers (BGP, PINP) were higher, while (3-CTX levels were lower (p < 0.05). The refracture rate was significantly reduced (5.26% vs. 17.11%) without differences in adverse reactions. Vertebral recovery correlated positively with bone formation markers and negatively with resorption markers. Denosumab combined with calcitriol improves bone metabolism, enhances vertebral restoration, and reduces refracture risk, demonstrating favorable efficacy and safety in elderly OVCF patients after PKP.
Glyphosate is the most widely used herbicide worldwide and is frequently applied in combination with dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D) in agricultural settings. Although regulatory reference values have been established for these compounds, concerns persist regarding their potential reproductive effects, particularly following prolonged exposure during sensitive developmental periods. This study evaluated whether chronic developmental exposure to glyphosate at European Union (EU) regulatory reference doses, namely the acceptable daily intake (ADI) and the no-observed-adverse-effect level (NOAEL), as well as to a mixture of glyphosate, dicamba, and 2,4-D at their respective EU ADI levels, induces hormonal and histopathological alterations in male reproductive organs. Pregnant Wistar rats were exposed from gestational day 6 through lactation, and male offspring continued treatment after weaning until postnatal day 111. At the end of the exposure period, serum testosterone levels, relative testis weight, and histopathological changes in testes and prostate were assessed. The herbicide mixture significantly decreased serum testosterone and increased relative testis weight. Histological analysis revealed progressive testicular and prostatic lesions, suggesting that developmental exposure to this herbicide mixture may disrupt male reproductive structure and endocrine homeostasis.
To ensure suitable powder flowability, compactability, and, implicitly, tablet quality, precompression studies are essential assessments carried out on tablet powder blends before final compression. Various investigations are performed on tablet formulation materials as part of precompression research. These analyses aim to evaluate the flow and compressibility of powder blends to determine whether their physicochemical properties meet processing requirements. This study reveals the influence of dry nanosuspension formulations on the physical characteristics of materials intended for the direct compression process. Six direct compression blends were prepared: three containing dry nanosuspensions of rivaroxaban (RIV), Poloxamer 188 (P188), and hydroxypropyl methylcellulose (HPMC), and three containing their simple physical mixtures. Various formulations based on microcrystalline cellulose and spray-dried lactose were analysed to evaluate their flowability and compressibility properties to determine their suitability for direct compression. It was concluded that a higher amount of HPMC and the use of the lyophilisation technique result in blends unsuitable for direct compression.
This study aimed to investigate the profiles of adipokines and cytokines found in urine, peritumoral adipose tissue, and subcutaneous adipose tissue from patients with breast and pancreatic cancer. We also wanted to understand their clinical and translational significance in relation to body mass index (BMI), systemic inflammation, and tumor markers. To achieve this, we measured levels of adiponectin, adipsin, RPB-4, MCP-1, IL-1 beta, IP-10, IL-10, IL-8, leptin, IL-6, IFN-gamma, resistin, and TNF-alpha in urine and the two types of adipose tissue using a LEGENDplex multiplex assay for flow cytometry. We observed notable differences across biological compartments for all mediators we examined, with urinary concentrations significantly higher than those in adipose tissue. The urinary leptin-to-adiponectin (L/A) ratio showed a significant positive correlation with body mass index and emerged as a more robust indicator of metabolic imbalance than either leptin or adiponectin alone. Tumor-infiltrating T-cell analysis, available for a small subset of patients, revealed marked inter-individual variability without permitting statistical inference.
The synthesis of new products by combining different physiologically active structural cores is of great interest to medicinal chemists due to the potential for synergistic effects, which can result in hybrids with enhanced pharmaceutical activities. Eight coumarin-chalcone hybrids were synthesized by reacting 4-hydroxy-3-acetylcoumarin with various substituted aromatic aldehydes. The structures of the synthesized products were fully characterized using spectral methods. Detailed assignment of H-1-and C-13-NMR resonances was achieved through a combination of 1H-1H COSY, NOESY, HSQC and HMBC experiments. Antioxidant activities were evaluated using the DPPH free radical scavenging assay.
Momordica charantia (MC), or bitter gourd, grows in tropical regions and has documented anti-diabetic, anti-ulcerogenic, antimicrobial, anti-tumour, anti-leukemic, and anti-inflammatory properties. This study evaluated the anti-inflammatory effects of polypeptide-K (PPK) and essential oil isolated from MC seeds in rat models of carrageenan-induced paw oedema and carrageenan-induced air pouch inflammation. In the paw oedema model, PPK and MC oil significantly reduced paw oedema volume, with effects comparable to indomethacin. In the air pouch model, PPK and MC oil suppressed total and absolute leukocyte, neutrophil, and monocyte counts, while PPK significantly reduced nitrite concentration. These findings suggest that PPK and MC oil inhibit acute inflammation by reducing leukocyte recruitment and nitrite production, and MC oil may additionally contribute through increased IL-10 during the late phase of inflammation. The results support the therapeutic potential of PPK and MC seed oil as candidate anti-inflammatory agents.
Ziziphus jujuba leaves are widely used in traditional medicine across Asia and parts of Europe, largely due to their antioxidant properties and their use in treating inflammatory conditions. This study aimed to validate the antioxidant and anti-inflammatory activities of Ziziphus jujuba leaves and to identify potential bioactive compound groups via solvent-polarity-based fractionation. Antioxidant activity of the ethanol extract and its fractions was evaluated in vitro using the 2,2-diphenyl-1-picrylhydraxyl (DPPH) radical scavenging assay, while the anti-inflammatory activity was assessed using the paw edema model in carrageenan-induced Wistar rats. The ethanol extract contained 43.70 +/- 1.78 mg gallic acid equivalents (GAE)/g extract of total phenolics and 19.49 +/- 0.88 mg quercetin equivalents (QE)/g extract of flavonoids. The ethanol extract and ethyl acetate fraction showed strong antioxidant activity with IC50 values of 89.76 & micro;g/mL and 78.07 & micro;g/mL, respectively. Both samples also demonstrated consistent anti-inflammatory effects between 180 and 360 minutes. These results indicate that bioactive antioxidant and anti-inflammatory compounds are mainly concentrated in the ethyl acetate fraction and, to a lesser extent, in the ethanol fraction.
