rss_2.0Acta Pharmaceutica FeedSciendo RSS Feed for Acta Pharmaceuticahttps://sciendo.com/journal/ACPHhttps://www.sciendo.comActa Pharmaceutica Feedhttps://sciendo-parsed.s3.eu-central-1.amazonaws.com/6470769f71e4585e08a9db88/cover-image.jpghttps://sciendo.com/journal/ACPH140216Prevalence and factors associated with potential clinically significant drug-drug interactions in patients with cardiovascular diseases at hospital admissionhttps://sciendo.com/article/10.2478/acph-2024-0038<abstract><title style='display:none'>Abstract</title> <p>Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally. It is estimated that 17.9 million people died from CVDs in 2019, which represents 32 % of all deaths worldwide. Cardiovascular drugs are the most common medical intervention for the prevention of cardiovascular events. CV medications have many benefits however their application is often complicated by multimorbidity and polypharmacy. Drug-drug interactions (DDIs) can lead to adverse drug events, hospitalizations, prolonged hospital stays, increased healthcare costs, and increased risk of mortality. Hospital admission provides an opportunity for pharmacotherapy analysis and for identifying DDIs which can jeopardize medication safety. The aim of this study is to determine the type and prevalence of potential clinically significant DDIs in patients with CVD and to examine factors associated with exposure to DDIs. A prospective study was conducted at the Dubrava University Hospital at the Clinic of Cardiology during a 6-month period (September 2023 – February 2024). Demographic, clinical and pharmacotherapy data were collected for each patient. The first prescribed pharmacotherapy was analyzed. The research was approved by the Hospital’s Ethics Committee and each patient involved in the study signed an informed consent. Lexicomp<sup>®</sup> Lexi-InteractTM Online (Lexi-Comp, Inc., USA) was used for DDI analysis. Poisson regression was used for regression analysis for determining risk factors associated with exposure to DDIs. Total of 151 patients admitted to Cardiology ward were included in the research, and the average age was 67 years. Patients had an average of 9 medications in their therapy and 8 diagnoses. Overall, 1268 potential clinically significant DDIs were determined, of which the most frequently determined interactions were grade C (90.9 %), then grade D (8.6 %) and grade X (0.6 %). CV medications were involved in 88 % DDIs. The most common interventions regarding identified DDIs included exclusion one of the drugs, dose adjustment, increased monitoring of signs of bleeding, cardiac disorders, hypoglycemia, CNS depression and rhabdomyolysis, blood pressure, markers of renal function and electrolyte status. Factors associated with the prevalence of potential clinically significant DDIs were decreased renal function, recent hospitalization, total number of comorbidities and polypharmacy. Specific comorbidities associated with DDIs were arrhythmia, heart failure, diabetes mellitus and disease of the respiratory system. A high prevalence of DDIs of CV medications in all categories of clinical significance was determined. Managing medication safety in specific patient groups with CVDs can represent a greater challenge regarding DDIs. Certain medical conditions, such as arrhythmia, heart failure, diabetes, and diseases of the respiratory system, multimorbidity, polypharmacy, impaired renal function and recent hospitalization are identified in this research as additional factors associated with DDIs occurrence in patients with CVDs at hospital admission. Hospital admission is one of the crucial points for managing medication safety. Clinical pharmacists should regularly analyze DDIs in prescribed pharmaco-therapy which enhances medication safety and also contributes to the quality of provided health care.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00382025-01-09T00:00:00.000+00:00Urban parks biowaste as a sustainable source of new antidiabeticshttps://sciendo.com/article/10.2478/acph-2024-0039<abstract><title style='display:none'>Abstract</title> <p>Biowaste produced in urban parks is composed of large masses of organic matter that is only occasionally used economically. In this work, extracts of six plants widely distributed in urban parks in Central Europe (<italic>Achillea millefolium</italic>, <italic>Cichorium intybus</italic>, <italic>Malva sylvestris</italic>, <italic>Medicago sativa</italic>, <italic>Plantago lanceolata</italic>, and <italic>Trifolium pratense</italic>), prepared using 10 % and 50 % ethanol, were screened for their antidiabetic and related properties. HPLC and UV-Vis analysis revealed the presence of caffeic acid, quercetin, luteolin, and apigenin derivatives. The extracts were active in DPPH antiradical, β-carotene-linoleic acid, ORAC, and reducing power assay. They inhibited lipoxygenase, collagenase, as well as heat-induced ovalbumin coagulation. They were also able to hinder carbohydrate degradation. For example, <italic>IC</italic><sub>50</sub> of anti-<italic>α</italic>-amylase activity of 10 % and 50 % ethanol extract of <italic>M. sativa</italic> extracts (204.10 ± 2.11 µg mL<sup>−1</sup> and 78.27 ± 0.99 µg mL<sup>−1</sup>, respectively) did not statistically differ from the activity of the positive control, acarbose (284.74 ± 3.81 µg mL<sup>−1</sup>). Similar results were observed for their anti-α-glucosidase activity. In most assays, the use of 50 % ethanol was shown to be better suited for the extraction of active metabolites. The results indicate that the biowaste obtained from urban parks represents a potential source of plant material for the preparation of high-value antidiabetic products.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00392025-01-09T00:00:00.000+00:00Optimization of the suspension procedure by Box-Behnken design for the determination of manganese, iron, and zinc in zeolite clinoptilolite with the TXRF system and insight into its antioxidant propertieshttps://sciendo.com/article/10.2478/acph-2024-0040<abstract><title style='display:none'>Abstract</title> <p>Zeolites are a large family of minerals and the most studied is the naturally occurring clinoptilolite. They possess anti-inflammatory, antioxidant, and detoxifying properties which makes them valuable for medicinal use. Element analysis of zeolite’s composition is necessary for its precise chemical characterization, and within this work development of a suspension method for the determination of manga nese, iron, and zinc by total reflection X-ray fluorescence spec-trometry (TXRF) was presented. The Box-Behnken design based on the response surface methodology was applied to determine the optimal sample preparation conditions. The significant variables such as sample amount, volume deposition, and dispersant were selected as critical variables. Based on the results obtained, sample suspensions were prepared by weighing 10 mg of the sample and adding 1 mL of 5 % Triton X-100 with 10 mL Ga as internal standard and deposition volume was set at 10 mL. The results obtained with TXRF were comparable with those obtained with the FAAS method, indicating that this technique can be used instead of the conventional methods. Using the best analytical conditions, the limits of detection for trace elements were in the range of 0.2–0.6 mg kg<sup>–1</sup>. Trueness and precision of the results, evaluated by CRM sample analysis, were in most cases acceptable with recoveries values in the range of 104.9–111.4 % and relative standard deviations of 2–10 % (. = 6). Zeolites showed no ability to quench free radicals nor the ability to influence dietary antioxidants.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00402025-01-09T00:00:00.000+00:00The impact of blood lipids and statins on renal function and mortality in patients with diabetic nephropathy: A meta-analysishttps://sciendo.com/article/10.2478/acph-2025-0002<abstract> <title style='display:none'>Abstract</title> <p>The aim of this study is to explore the impact of blood lipids and statins on renal function and all-cause mortality in patients with diabetic nephropathy (DN). PubMed, Embase, Web of Science, and Cochrane Library were systematically searched until April 9, 2024, for relevant studies of blood lipids and statins on renal function and all-cause mortality in patients with DN. After the selection, total cholesterol levels (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), serum creati-nine (SCR), end-stage renal disease (ESRD), and all-cause mortality indexes were extracted for finally meta-analysis. In total, 25 papers containing 21,411 patients with DN were finally included in this study. Levels of TC and LDL-C, which are continuous variables, were higher in DN patients who developed ESRD [TC/weighted mean difference (WMD) = 0.517, 95 % confidence interval (CI): (0.223, 0.812), <italic>p =</italic> 0.001; LDL-C/WMD = 0.449, 95%CI: (0.200, 0.698), <italic>p</italic> &lt; 0.001]. In addition, this study also observed that statins may reduce UAE levels [WMD = –46.814, 95% CI: (–71.767, –21.861), <italic>p</italic> &lt; 0.001]. Finally, the survey indicated that statins may be associated with an ESRD reduction [HR = 0.884, 95% CI: (0.784, 0.998), <italic>p</italic> = 0.045]. Blood lipids, particularly TC and LDL-C, may slow the progression of DN to ESRD. Besides, statins may protect the kidneys by lowering the excretion of UAE levels and reducing the risk of ESRD. Based on the above outcomes, the findings of this study provided robust evidence-based medical support for the future prevention, surveillance, and management of DN.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2025-00022024-12-17T00:00:00.000+00:00Integrating network pharmacology and model to reveal the cardiovascular protective effects of kaempferol-3--rutinoside on heart failurehttps://sciendo.com/article/10.2478/acph-2025-0001<abstract> <title style='display:none'>Abstract</title> <p>Kaempferol-3-<italic>O</italic>-rutinoside (KR) has an excellent cardioprotective effect, but its mechanism of action is not clear. Network pharmacology was used to predict the signaling pathways, whereas molecular docking was used for preliminary validation of KR binding to targets. AMI model rats with ligated left anterior descending coronary arteries were established. HE staining was used to detect pathological changes, and ELISA was used to detect the expression of TNF-α and IL-6. Network pharmacology results showed PI3K-AKT signaling pathway may be the main mechanism, and molecular docking predicted that KR could bind strongly to the PI3K and AKT. KR could significantly reduce cardiac pathological changes, decrease the level of TNF-α and IL-6, and enhance the mRNA and protein expressions of PI3K and AKT. KR ameliorates HF after AMI by enhancing the expressions of PI3K and AKT, which will be helpful in elucidating the mechanism of KR through multiple techniques.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2025-00012024-12-17T00:00:00.000+00:00Cloning, expression, and purification of recombinant AKR1D1 for therapeutic applicationshttps://sciendo.com/article/10.2478/acph-2025-0003<abstract> <title style='display:none'>Abstract</title> <p>AKR1D1, a key enzyme in the aldo-keto reductase superfamily, plays a dual role in both steroid metabolism and bile acid synthesis by catalyzing the NADPH-dependent reduction of carbon-carbon double bonds, specifically converting 3-ketosteroid hormones into 5β-steroids. Positioned at the critical intersection of steroid hormone and bile acid metabolism, AKR1D1 has the potential to profoundly influence metabolic homeostasis and drug metabolism. Despite its importance, the enzyme’s therapeutic implications and role in drug metabolism remain underexplored. This study presents an optimized methodology for the cloning, expression, and purification of AKR1D1 using an <italic>Escherichia coli</italic> expression system. We identified optimal conditions for ligation and precise DNA sequencing, emphasizing the need for lower DNA concentrations and higher purity. Protein expression was evaluated in <italic>E. coli</italic> strains BL21 and Rosetta, with the highest yields achieved under extended incubation at 25 °C with controlled IPTG concentrations. Using freshly transformed cells was essential for maintaining consistent protein expression. The enzyme’s activity was confirmed using a spectrofluorometric assay, demonstrating efficient reduction of testosterone to 5β-DHT. This optimized methodology facilitates the production of AKR1D1 with high specific activity, establishing a valuable platform for future research. It enables a deeper investigation into AKR1D1’s contributions to drug metabolism and its therapeutic potential.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2025-00032024-12-17T00:00:00.000+00:00Advancements in electron paramagnetic resonance (EPR) spectroscopy: A comprehensive tool for pharmaceutical researchhttps://sciendo.com/article/10.2478/acph-2024-0037<abstract><title style='display:none'>Abstract</title> <p>Electron paramagnetic resonance (EPR) spectroscopy has long been established across various scientific disciplines for characterizing organic radicals, organometallic complexes, protein structures and dynamics, polymerization processes, and radical degradation phenomena. Despite its extensive utility in these areas, EPR spectroscopy’s application within pharmaceutical science has historically been constrained, primarily due to factors such as high equipment costs, a steep learning curve, complex spectral deconvolution and analysis, and a traditional lack of emphasis on single-electron chemistry in pharmaceutical research. This review aims to provide a thorough examination of EPR spectroscopy’s applications in analyzing a wide array of para-magnetic species relevant to pharmaceutical research. We detail how EPR spectroscopy can be employed to assess free radical scavenging properties in pharmaceutical compounds, elucidate drug mechanisms of action, and explore pharmacokinetics. Additionally, we investigate the role of free radicals in drug-induced toxicity and drug-membrane interactions, while also covering the application of EPR spectroscopy in drug delivery research, advanced studies of metallodrugs, and monitoring of oxygen levels in biological systems through EPR oximetry. The recent advancements in the miniaturization of EPR spectro meters have paved the way for their application in <italic>on-site</italic> and <italic>in-line</italic> mo nitoring during the manufacturing process and quality control of pharmaceutical substances and final drug formulations due to being the only direct and non-invasive detection technique for radical detection.</p> <p>Through these discussions, we highlight the substantial contributions of EPR spectroscopy to the advancement of pharmaceutical sciences.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00372025-01-09T00:00:00.000+00:00Complete blood count parameters and inflammation-related biomarkers in patients with colorectal carcinomahttps://sciendo.com/article/10.2478/acph-2024-0036<abstract><title style='display:none'>Abstract</title> <p>The aim of this study was to determine whether there are differences in complete blood count parameters (CBC) and inflammation-related biomarkers, MPV/PC, PLR, NLR, LWR, LMR, NMR, and LCR, among patients with colorectal carcinoma (CRC) and patients with colorectal adenomas. The study included 155 patients who were divided into two groups according to histopathological analysis – 74 adenomas patients and 81 CRC patients. A routine examination of CBC was conducted on Sysmex XN1000 whereas CRP was measured on Alinity ci-series. Statistical analysis was performed by ROC curve analysis using MedCalc Statistical Software. In CRC patients, hemoglobin concentration, hematocrit, MCV, MCH, and MCHC were lower, while RDW was higher (<italic>p </italic> &lt; 0.001), compared to patients with adenomas. Total leukocyte count (<italic>p </italic>= 0 .006), absolute neutrophils (<italic>p</italic> = 0.005), and absolute monocytes (<italic>p </italic> = 0.007) were lower while relative eosinophils (<italic>p </italic>= 0.001) and relative basophils (<italic>p </italic> = 0.001) were higher in CRC patients. Platelet count (<italic>p </italic> &lt; 0.001) was significantly higher and MPV (<italic>p </italic> = 0.003) was significantly lower in CRC patients. Furthermore, MPV/PC (<italic>p </italic> &lt; 0.001) was significantly lower and PLR (<italic>p </italic> &lt; 0.001) was significantly higher in CRC. Moreover, Receiver Operating Characteristic (ROC) analysis revealed poor diagnostic accuracy, for all tested parameters (AUC was 0.7 or less). PC, MPV, MPV/PC, and PLR were significantly different between study groups, but ROC analysis revealed poor diagnostic accuracy. Lower hemo globin levels in CRC patients are possibly due to more frequent and excessive bleeding. Higher levels of basophils and eosinophils in CRC patients are indicators of inflammatory reaction, which is linked to CRC.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00362025-01-09T00:00:00.000+00:00Phenolic content and antioxidant activity of Croatian and German honeyhttps://sciendo.com/article/10.2478/acph-2024-0031<abstract><title style='display:none'>Abstract</title> <p>Since honey has a therapeutic role in the treatment of many diseases, we investigated the content of phenolic compounds and the antioxidant activity in acacia (<italic>Robinia pseudoacacia</italic> L.), chestnut (<italic>Castanea sativa</italic> Mill.) and lime-tree (<italic>Tilia </italic>spp.) honey originating from Croatia and Germany. Total phenols, flavonols, and flavanols contents were observed at higher levels in Croatian <italic>Castanea</italic> honey compared to German <italic>Castanea</italic> honey. Significant higher values of total flavanols and hydroxycinnamic acids were measured in Croatian <italic>Tilia</italic> honey compared to German <italic>Tilia</italic> honey. For <italic>Robinia</italic> honey, significantly higher values of total phenols and flavonols were observed in almost all Croatian honey samples compared to German honey. Croatian honey samples had higher antioxidant activity compared to German honey samples with most tested methods. The highest total phenols, total flavanols, ABTS, DPPH, and FRAP values were measured in <italic>Castanea</italic> honey, then in <italic>Robinia</italic> honey, and the lowest values in <italic>Tilia</italic> honey samples. With new developed HPLC method, pinobanksin, pinocembrin, and chrysin were identified in the majority of honey samples. Our results imply that both botanical and geographical origin influence the final quality of phenolic compounds and antioxidant activity in honey. A high positive correlation between the results of antioxidant activity and polyphenols was detected.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00312025-01-09T00:00:00.000+00:00Total phenolic content, flavonoid content and antioxidant potential of and related species from Croatia and considerations regarding their pharmaceutical significancehttps://sciendo.com/article/10.2478/acph-2024-0032<abstract><title style='display:none'>Abstract</title> <p>Extracts obtained from common butterbur (<italic>Petasites hybridus</italic>), standardized to petasins, are existing pharmaceutical options for the treatment and/or prevention of allergic rhinitis (leaves) and migraine (rhizomes). In this study, the total phenolic content, flavonoid content, and antioxidant potential of ten samples of Croatian <italic>Petasites</italic> species (four <italic>P. hybridus</italic>, four <italic>P. albus</italic>, one <italic>P. kabli kianus</italic>, and one <italic>P. paradoxus</italic>) obtained by ultrasound-assisted extraction of leaves were compared. The total phenolic content (Folin-Ciocalteu assay) of methanolic leaf extracts ranged from 4.43 ± 0.09 to 10.76 ± 0.60 mg gallic acid equivalent g<sup>−1</sup> dry mass (mg GAE g<sup>−1</sup> DM) for <italic>P. hybridus</italic> and from 6.66 ± 0.43 to 19.92 ± 2.90 mg GAE g<sup>−1</sup> DM for <italic>P. albus</italic> samples, while those of <italic>P. kablikianus</italic> and <italic>P. paradoxus</italic> were equal to 7.56 ± 0.17 mg GAE g<sup>−1</sup> DM and 10.22 ± 0.46 mg GAE g<sup>−1</sup> DM, respectively. Flavonoid content (AlCl<sub>3</sub> assay) varied between 2.51 ± 0.10 and 4.03 ± 0.08 mg quercetin equivalent g<sup>−1</sup> dry mass (mg QE g<sup>−1</sup> DM) for <italic>P. hybridus</italic> and between 2.21 ± 0.09 and 5.22 ± 0.02 mg QE g<sup>−1</sup> DM for <italic>P. albus</italic> samples, while those of <italic>P. kablikianus</italic> and <italic>P. paradoxus</italic> were equal to 5.59 ± 0.05 mg QE g<sup>−1</sup> DM and 5.50 ± 0.09 mg QE g<sup>−1</sup> DM, respectively. Antioxidant potential was in high correlation with total phenolic content (<italic>r</italic> = 0.93, <italic>p</italic> &lt; 0.001). Due to the expected contribution of plant polyphenols and flavonoids to the activity of butterbur extracts and their observed great variabilities, determining the content of these compounds may be of interest to the pharmaceutical industry.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00322025-01-09T00:00:00.000+00:00Fall risk-increasing drugs and associated health outcomes among community-dwelling older patients: A cross-sectional study in Croatian cohort of the EuroAgeism H2020 projecthttps://sciendo.com/article/10.2478/acph-2024-0034<abstract><title style='display:none'>Abstract</title> <p>Our study aimed to assess the prevalence of fall risk-increasing drugs (FRIDs) in a sample of community-residing older patients in Croatia and its association with negative health outcomes. An observational, cross-sectional study was conducted on older patients (65+) visiting community pharmacies in three regionally different study sites in Croatia. Data were collected using a questionnaire developed for that purpose and included components of comprehensive geriatric assessment. Prevalence of FRIDs was identified using the “Screening Tool of Older Persons Prescriptions in older adults with high fall risk” (STOPPFall). In the sample of 407 participants (median age 73 (IQR 69–70) years; 63.9 % females), 79.1 % used at least one FRID. The most common drug classes were diuretics, benzodiazepines, and opioids (in 51.1 %, 38.1 %, and 17.2 % participants, respectively). More FRIDs were prescribed to the oldest old patients (85+) and participants from poorer regions of Croatia (Slavonia) (<italic>p</italic> &lt; 0.05). Exposition to FRIDs was identified as the significant risk factor associated with falls (OR = 1.24 (1.04–1.50); <italic>p</italic> = 0.020) and higher health-care utilization (OR = 1.29 (1.10–1.51); <italic>p</italic> = 0.001). Our study highlights the need for rationalization of FRID use. To reduce the unnecessary exposure to FRIDs in older adults, health-care professionals must consider high individualization of medication schemes regarding selection, dosing, and combinations of only necessary FRIDs.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00342025-01-09T00:00:00.000+00:00Light-induced rearrangement from macrocyclic to bicyclic lactam: A case study of -chlorinated laurolactamhttps://sciendo.com/article/10.2478/acph-2024-0035<abstract><title style='display:none'>Abstract</title> <p>Converting macrocycle lactams into bicyclic lactams is proposed as an additional way to further increase the metabolic stability of peptide-based drugs. Unfortunately, the synthesis of bicyclic lactams has to start almost from scratch. This study explores the Hofmann-Löffler-Freytag (HLF) reaction mechanism and products as a potential late-stage functionalisation strategy for facile conversion of macrocyclic to bicyclic ring. Laurolactam, a macrocyclic amide, exhibits significant potential for transformation into bioactive bicyclic structures with smaller, β-, γ-, δ-, and ε-lactam rings, further increasing rigidity and hydrolytic stability. With irradiation provided by a 370 nm lamp, light-induced rearrangement reaction was monitored using nuclear magnetic resonance (NMR), while involved radical intermediates were trapped using <italic>N</italic>-<italic>tert</italic>-butyl-α-phenylnitrone (PBN) spin-trap and characterised <italic>via</italic> EPR. While only two radical adduct types were identified in the electron para magnetic resonance (EPR) (<italic>C</italic>-centered radical and chlorine radical), all eight possible products are observed in the NMR. Quantum chemical calculations provide deeper insights into reaction thermodynamics and kinetics, explaining why the <italic>N</italic>-centered radical was not observed. This research highlights the feasibility of using the HLF reaction to transform macrocyclic lactams into stable bicyclic drug candidates, paving the way for new therapeutic developments.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00352025-01-09T00:00:00.000+00:00Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybridshttps://sciendo.com/article/10.2478/acph-2024-0033<abstract><title style='display:none'>Abstract</title> <p>The poor prognosis of glioblastoma multiforme, inadequate treatment options, and growing drug resistance urge the need to find new effective agents. Due to the significant anti-cancer potential of harmicens, hybrid compounds which comprise harmine/β-carboline and ferrocene moiety, we investigated their antiglioblastoma potential <italic>in vitro</italic> and mechanism of action (inhibition of DYRK1A, Hsp90, anti-oxidative activity). The results have shown that triazole-type harmicens, namely <bold>5</bold>, with a ferrocene moiety in C-3 position of the β-carboline ring (<italic>IC</italic><sub>50</sub> = 3.7 ± 0.1 µmol L–1, SI = 12.6) and ., the C-6 substituted harmicene (<italic>IC</italic><sub>50</sub> = 7.4 ± 0.5 µmol L–1, SI = 5.8) exert remarkable activity and selectivity against human malignant glioblastoma cell line (U251) <italic>in vitro</italic>. On the other hand, amide-type harmicens <bold>10</bold>, <bold>12</bold>, and <bold>14</bold> exhibited strong, but non-selective activity, in the low micro-molar range. Mechanistic studies revealed that among active compounds, amide-type harmicens <bold>12</bold> and <bold>14</bold> inhibit DYRK1A and Hsp90 CTD, whereas compound <bold>14</bold> showed pronounced antioxidative activity. Therefore, the antiproliferative activity of harmicens might be a combination of complex molecular interactions.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00332025-01-09T00:00:00.000+00:00Analysis of doxorubicin and fullerenol in rat serum by micellar electrokinetic capillary chromatographyhttps://sciendo.com/article/10.2478/acph-2024-0026<abstract> <title style='display:none'>Abstract</title> <p>A new micellar electrokinetic capillary chromatographic (MEKC) method has been developed and optimized for simultaneous quantitation of doxorubicin (Dox) and fullerenol (Frl) in rat serum. The separation was carried out in a capillary (48.5–40 cm to the detector – 50 µm id fused-silica capillary with bubble cell, 150 µm) at an applied voltage of 25 kV and temperature of 25 °C. For the background electrolyte 10 mmol L<sup>–</sup><sup>1</sup> borate buffer pH 9.3 plus 15 mmol L–1 phosphate buffer pH 7.0 (with the final pH of the mixture adjusted to 7.0 with HCl), with added 10 % (<italic>V</italic>/<italic>V</italic>) methanol, and 15 mmol L–1 sodium dodecyl sulfate as a surfactant, were used. The hydrodynamic injection was carried out at 5.0 kPa during the period of 100 s. Linear calibration curves were established over the concentration range 0.5–500.0 mg L<sup>–</sup><sup>1</sup> for Dox and 10.0–500.0 mg L<sup>–</sup><sup>1</sup> for Frl (at 234 nm). The proposed MEKC procedure was fully validated and applied for the deter mination of Dox and Frl in Wistar rats after intra pe ritoneal administration of both molecules.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00262024-09-14T00:00:00.000+00:00Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPshttps://sciendo.com/article/10.2478/acph-2024-0025<abstract> <title style='display:none'>Abstract</title> <p>Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L–1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00252024-09-14T00:00:00.000+00:00The tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liverhttps://sciendo.com/article/10.2478/acph-2024-0027<abstract> <title style='display:none'>Abstract</title> <p>Lenvatinib is an orally effective tyrosine kinase inhibitor used to treat several types of tumors, including progressive, radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma. Although this drug is increasingly used in therapy, its metabolism and effects on the organism are still not described in detail. Using the rat as an experimental animal model, this study aimed to investigate the metabolism of lenvatinib by rat microsomal enzymes and cytochrome P450 (CYPs) enzymes recombinantly expressed in Supersomes<sup>TM</sup> <italic>in vitro</italic> and to assess the effect of lenvatinib on rat CYP expression <italic>in vivo</italic>. Two metabolites, <italic>O</italic>-desmethyl lenvatinib, and lenvatinib <italic>N</italic>-oxide, were produced by rat CYPs <italic>in vitro</italic>. CYP2A1 and 2C12 were found to be the most effective in forming <italic>O</italic>-desmethyl lenvatinib, while CYP3A2 was found to primarily form lenvatinib <italic>N</italic>-oxide. The administration of lenvatinib to rats caused changes in the expression of mRNA and protein, as well as the activity of various CYPs, particularly in an increase in CYP1A1. Thus, the administration of lenvatinib to rats has an impact on the level of CYPs.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00272024-09-14T00:00:00.000+00:00Efficacy of sorafenib plus transcatheter arterial chemoembolization in treating hepatocellular carcinoma with portal vein tumor thrombosis: A meta-analysishttps://sciendo.com/article/10.2478/acph-2024-0019<abstract> <title style='display:none'>Abstract</title> <p>This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28<sup>th</sup> Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507–0.685, <italic>p</italic> &lt; 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205–0.553, <italic>p</italic> &lt; 0.001; I<sup>2</sup> = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555–2.839, <italic>p</italic> &lt; 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126–2.126, <italic>p</italic> = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, <italic>p</italic> &lt; 0.001; I<sup>2</sup> = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00192024-09-14T00:00:00.000+00:00Personalization of thiopurine therapy: Current recommendations and future perspectiveshttps://sciendo.com/article/10.2478/acph-2024-0030<abstract> <title style='display:none'>Abstract</title> <p>Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. This review presents the latest guidelines for thiopurine administration, highlighting the importance of individualized therapy guided by pharmacogenomics. It emphasizes dose adjustment based on nudix hydrolase 15 (<italic>NUDT15</italic>) and thiopurine <italic>S</italic>-methyltransferase (<italic>TPMT</italic>) genotype, along side thiopurine <italic>S</italic>-methyltransferase activity and thiopurine metabolic profile. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00302024-09-14T00:00:00.000+00:00PPIA, HRPT1, and PGK1 genes as the appropriate combination for RT-qPCR normalization in alveolar and femoral bone remodeling in olanzapine-treated ratshttps://sciendo.com/article/10.2478/acph-2024-0029<abstract> <title style='display:none'>Abstract</title> <p>Reliable gene expression analysis in bone remodeling studies requires an appropriate selection of internal controls, <italic>i.e.</italic> stable reference genes for the normalization of quantitative real-time PCR (RT-qPCR), the most common method used for quantifying gene expression measurements. Even the most widely used reference genes can have variable expression under different experimental conditions, or in different tissue types or treatment regimes, so selecting appropriate controls is a key step in ensuring reliable results. The aim of this research was to identify the most stable reference gene(s) for the study of olanzapine modulated bone remodeling in rats. RNA was isolated from the maxillary alveolar and femoral bones of olanzapine or placebo-treated Wistar rats and transcribed to cDNA. The expression of 12 candidate reference genes was assessed by RT-qPCR. Their expressions were analysed using GeNorm, NormFinder, BestKeeper and delta Ct algorithms, and by the comprehensive ranking method. <italic>PPIA, HRPT1</italic> and <italic>PGK1</italic> were the most stably expres sed reference genes and the combination of the three genes was optimal for normalization. This study is the first to identify the optimal reference genes for research in olanzapine-exposed rats, which serve as a pivotal benchmark for enhancing the accuracy and reliability of future RT-qPCR expression in bone studies.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00292024-09-14T00:00:00.000+00:00Synthesis and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s)https://sciendo.com/article/10.2478/acph-2024-0024<abstract> <title style='display:none'>Abstract</title> <p>In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from <italic>Streptococcus pneumoniae</italic>. Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/acph-2024-00242024-09-14T00:00:00.000+00:00en-us-1