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New methods for assaying trimetazidine dihydrochloride on the basis of thin layer chromatography and spectrophotometry are proposed and compared in the paper. In HPTLC/UV-densitometry, separation is achieved by using a mobile phase composed of ammonia-methanol (30:70, V/V) on silica gel HPTLC plates F254. Quantification using a non-linear calibration curve is accomplished by densito-metric detection at 230 nm. Derivative spectrophotometric determination of trimetazidine dihydrochloride is carried out from the fourth derivative of the absorbance at 233 nm in peak-zero mode. Statistical comparison led to the conclusion that there is no significant difference between the two studied methods and, moreover, that they demonstrate satisfactory accuracy and precision for routine applications.

Background: Molecular classification, tumor diameter, Ki67 expression, and brachytherapy administration still act as the most potent potential predictors of breast cancer recurrence and overall survival. Methods: Over the period of 23 months, we included in the study 92 invasive breast cancer (IBrC) patients initially diagnosed at the Clinical Ward of Breast Cancer and Reconstructive Surgery, Oncology Center in Bydgoszcz, Poland. The probability of disease-free survival (DFS) and overall survival (OS) in relation to potential prognostic factors for the patients were determined using a Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses evaluated the predictive factors of IBrC patients. The investigation of the potential prognostic model's accuracy was analyzed using the ROC curve. Results: Patients with tumor size < 2 cm, Ki67 expression < 20%, luminal-A molecular subtype, and extra-dose brachytherapy boost administration displayed the most favorable prognosis according to breast cancer disease-free survival and overall survival. The estimated 5 year probability of DFS and OS rates in women with tumor diameter < 2 cm were 89% and 90%, respectively. In tumor diameter > 2 cm, the estimated 5 year probability of DFS was 73% and OS was 76%. Interestingly, the tumor diameter of 1.6 cm with a specificity of 60.5% and a sensitivity of 75% occurred as the best threshold point to differentiate patients with cancer recurrence from those without cancer progression. Conclusions: Our study provides essential information on the clinicopathological profile and future outcomes of early stage IBrC patients. Furthermore, the tumor diameter cut-off value of 1.6 cm discriminating between disease recurrence and those without disease progression patients represents an innovative direction for further research.

Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.

Several studies have indicated that COVID-19 can lead to alterations in blood rheology, including an increase in red blood cell aggregation. The precise mechanisms behind this phenomenon are not yet fully comprehended. The latest findings suggest that erythrocyte aggregation significantly influences microcirculation, causes the formation of blood clots in blood vessels, and even damages the endothelial glycocalyx, leading to endothelial dysfunction. The focus of this research lies in investigating the cellular factors influencing these changes in aggregation and discussing potential causes and implications in the context of COVID-19 pathophysiology. For this purpose, the aggregation of erythrocytes in a group of 52 patients with COVID-19 pneumonia was examined in a 70 kDa Dextran solution, which eliminates the influence of plasma factors. Using image analysis, the velocities and sizes of the formed aggregates were investigated, determining their porosity. This study showed that the process of erythrocyte aggregation in COVID-19 patients, independent of plasma factors, leads to the formation of more compact, denser, three-dimensional aggregates. These aggregates may be less likely to disperse under circulatory shear stress, increasing the risk of thrombotic events. This study also suggests that cellular aggregation factors can be responsible for the thrombotic disorders observed long after infection, even when plasma factors have normalized. The results and subsequent broad discussion presented in this study can contribute to a better understanding of the potential complications associated with increased erythrocyte aggregation.

Fluorescence lifetime measurements of blood or plasma offer valuable insights into the microenvironment and molecular interactions of fluorophores, particularly concerning albumin. Neutrophil- and hypoxia-induced oxidative stress in COVID-19 pneumonia patients leads to hyperinflammation, various oxidative modifications of blood proteins, and potential alterations in the fluorescence lifetime of tryptophan-containing proteins, especially albumin. The objective of this study was to investigate the efficacy of time-resolved fluorescence spectroscopy of blood and plasma as a prompt diagnostic tool for the early diagnosis and severity assessment of COVID-19-associated pneumonia. This study examined a cohort of sixty COVID-19 patients with respiratory symptoms. To investigate whether oxidative stress is the underlying cause of the change in fluorescence lifetime, human serum albumin was treated with chloramine T. The time-resolved spectrometer Life Spec II (Edinburgh Instruments Ltd., Livingston, UK), equipped with a sub-nanosecond pulsed 280 nm diode, was used to measure the fluorescence lifetime of blood and plasma. The findings revealed a significant reduction in the fluorescence lifetime of blood (diluted 200 times) and plasma (diluted 20 times) at 360 nm in COVID-19 pneumonia patients compared with their respective values recorded six months post-infection and those of healthy individuals. Significant negative correlations were observed between the mean fluorescence lifetime of blood and plasma at 360 nm and several severity biomarkers and advanced oxidation protein products, while a positive correlation was found with albumin and the albumin-globulin ratio. The time-resolved fluorescence spectroscopy method demonstrates the potential to be used as a preliminary screening technique for identifying patients who are at risk of developing severe complications. Furthermore, the small amount of blood required for the measurements has the potential to enable a rapid fingerstick blood test.

Pseudomonas aeruginosa is an opportunistic pathogen encoding several virulence factors in its genome, which is well-known for its ability to cause severe and life-threatening infections, particularly among cystic fibrosis patients. The organism is also a major cause of nosocomial infections, mainly affecting patients with immune deficiencies and burn wounds, ventilator-assisted patients, and patients affected by other malignancies. The extensively reported emergence of multidrug-resistant (MDR) P. aeruginosa strains poses additional challenges to the management of infections. The aim of this study was to compare the incidence rates of selected virulence-factor-encoding genes and the genotype distribution amongst clinical multidrug-sensitive (MDS) and MDR P. aeruginosa strains. The study involved 74 MDS and 57 MDR P. aeruginosa strains and the following virulence-factor-encoding genes: lasB , plC H , plC N , exoU , nan1 , pilA, and pilB . The genotype distribution, with respect to the antimicrobial susceptibility profiles of the strains, was also analyzed. The lasB and plC N genes were present amongst several P. aeruginosa strains, including all the MDR P. aeruginosa , suggesting that their presence might be used as a marker for diagnostic purposes. A wide variety of genotype distributions were observed among the investigated isolates, with the MDS and MDR strains exhibiting, respectively, 18 and 9 distinct profiles. A higher prevalence of genes determining the virulence factors in the MDR strains was observed in this study, but more research is needed on the prevalence and expression levels of these genes in additional MDR strains.

The aim of this study was to investigate the aggregation of red blood cells (RBCs) suspended in dextran solution at various levels of molecular mass. Dextran solutions at molecular mass 40, 70, 100 and 500 kDa at concentration from 2 to 5 g/dL were used to suspend the RBCs. The radius and velocity of sedimenting RBC aggregates were investigated using image analysis. The radius and sedimentation velocity of aggregates increased initially, then decreased after achieving maxima. The maximal velocity of RBC aggregates showed a bell-shaped dependence on dextran molecular mass and concentration, whereas maximal radius showed monotonic increase with both factors. Difference between aggregate and solution density was estimated using aggregate radius and sedimentation velocity and dextran solution viscosity, and was consistent across most molecular mass and concentration levels. This allowed to calculate the porosity of aggregates and to show that it monotonically decreased with the increase in the solution density, caused by the increase in the dextran concentration. The results provide insight into the RBC aggregation process in solutions of proteins of different size, reflecting various pathological conditions. The currently reported data can be potentially applied to specific pathophysiological conditions giving an interpretation that is not yet fully discussed in the literature., (© 2022. The Author(s).)

Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.

A method of rapidly pointing out the risk of developing persistent pulmonary fibrosis from a sample of blood is extraordinarily needed for diagnosis, prediction of death, and post-infection prognosis assessment. Collagen scar formation has been found to play an important role in the lung remodeling following SARS-CoV-2 infection. For this reason, the concentration of collagen degradation products in plasma may reflect the process of lung remodeling and determine the extent of fibrosis. According to our previously published results of an in vitro study, an increase in the concentration of type III collagen degradation products in plasma resulted in a decrease in the fluorescence lifetime of plasma at a wavelength of 450 nm. The aim of this study was to use time-resolved fluorescence spectroscopy to assess pulmonary fibrosis, and to find out if the lifetime of plasma fluorescence is shortened in patients with COVID-19. The presented study is thus far the only one to explore the fluorescence lifetime of plasma in patients with COVID-19 and pulmonary fibrosis. The time-resolved spectrometer Life Spec II with the sub-nanosecond pulsed 360 nm EPLED® diode was used in order to measure the fluorescence lifetime of plasma. The survival analysis showed that COVID-19 mortality was associated with a decreased mean fluorescence lifetime of plasma. The AUC of mean fluorescence lifetime in predicting death was 0.853 (95% CI 0.735−0.972, p < 0.001) with a cut-off value of 7 ns, and with 62% sensitivity and 100% specificity. We observed a significant decrease in the mean fluorescence lifetime in COVID-19 non-survivors (p < 0.001), in bacterial pneumonia patients without COVID-19 (p < 0.001), and in patients diagnosed with idiopathic pulmonary fibrosis (p < 0.001), relative to healthy subjects. Furthermore, these results suggest that the development of pulmonary fibrosis may be a real and serious problem in former COVID-19 patients in the future. A reduction in the mean fluorescence lifetime of plasma was observed in many patients 6 months after discharge. On the basis of these data, it can be concluded that a decrease in the mean fluorescence lifetime of plasma at 450 nm may be a risk factor for mortality, and probably also for pulmonary fibrosis in hospitalized COVID-19 patients.

Three Salmonella enterica strains were used in the study (serovars: S. enteritidis , S. typhimurim and S. virchow ). This study evaluated the efficacy of radiant catalytic ionization (RCI) and ozonation against Salmonella spp. on eggshell (expressed as log CFU/egg). The egg surface was contaminated three different bacterial suspension (10 3 CFU/mL, 10 5 CFU/mL and 10 8 CFU/mL) with or without poultry manure. Experiments were conducted at 4 °C and 20 °C in three different time period: 30 min, 60 min and 120 min. Treatment with RCI reduced Salmonella numbers from 0.26 log CFU/egg in bacterial suspension 10 8 CFU/mL, 4 °C and 20 °C, with manure for 30 min to level decrease in bacteria number below the detection limit (BDL) in bacterial suspension 10 5 CFU/mL, 20 °C, with or without manure for 120 min. The populations of Salmonella spp. on eggs treated by ozonizer ranged from 0.20 log CFU/egg in bacteria suspension 10 8 CFU/mL, 20 °C, with manure for 30 min to 2.73 log CFU/egg in bacterial suspension 10 5 CFU/mL, 20 °C, with manure for 120 min. In all treatment conditions contamination with poultry manure decrease effectiveness the RCI and ozonation. In summary, RCI technology shows similar effectiveness to the ozonation, but it is safer for poultry plant workers and consumers.

The positively charged products of Cisplatin hydrolysis can form bonds with Guanine and Adenine, showing the ability to crosslink with nucleobases within the double helical DNA, and leading to apoptosis of the neoplastic cell. It has been proved that the presence of chemicals other than nucleobases, compound of aromatic rings with a nitrogen lone pair on the ring, such as B vitamins, may have a competitive character in relation to a chemotherapeutic drug. A theoretical study confirms the stability of bonds formed not only between Cisplatin and Guanine/Adenine but also Cisplatin and B vitamins, namely Thiamine (vit.B1), Niacin (vit.B3), Riboflavin (vit.B2) and Pyridoxal phosphate (vit.B6). That is why it seems to be justified to conduct the research on the physicochemical, thermochemical and optical properties of mono and diaqua complexes of Cisplatin with nucleobases and B vitamins. Equally important is carrying out such research as spectroscopic measurements, bond order analysis and vibrational analysis of the studied complexes. The complexation reaction is spontaneous and thermodynamically favored with the high electronegativity value, a shift of the electron density from the metal zone towards organic compounds, a reduction the value of gap parameter and a shift of the maximum absorbance Δλ ABS towards longer wavelengths. Moreover, the performed density variation upon photoexcitation showed the contributions from HOMO→LUMO transition, where the maximum of the absorption band shifts towards shorter wavelengths compared to the cisPt derivatives, thereby lowering the photoexcitation energy. The formation of complexes causes the reduction of energy gap (ΔE gap ) values and show higher kinetic stability with high values of gap. The bonding energies between Cisplatin and the target molecules were performed. Cisplatin forms the strongest bonds with Guanine and Pyridoxal phosphate (vit.B6). The vibrations of Pt-N7 bond in complexes occur in the low range of frequencies with low intensities. Only in case of nucleobases appeared vibrations of Pt-N 7 in high frequencies. The highest intensity is shown by symmetry and asymmetry stretching vibrations of H-O(H 2 O) bonds in the high range of frequencies. The vibrations related with ammonium groups (NH 3 ) of great importance appear in the medium and high range of frequencies. The complexes with Guanine show the highest intensities. A theoretical IR spectra were studied. The obtained calculated IR spectra for native nucleobases and vitamins from B group were compared with their experimental FT-IR. So the conducted research provides theoretical knowledge in practical terms regarding the physicochemical and spectral properties of the formed Cisplatin complexes with both nucleobases and B vitamins. Theoretical and partially experimental studies of the molecular and electronic structure or prediction of spectroscopic characteristics are quite useful for better understanding of the reactivity of this drug with physiological target molecules., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the usefulness of time-resolved fluorescence spectroscopy in the evaluation of the oxidative processes in human plasma. To investigate the impact of oxidative stress on the fluorescence of plasma, five studied markers (thiobarbituric acid-reactive substances, ischemia modified albumin, carbonyl groups, hydrogen peroxide, advanced oxidation protein products) were chosen as oxidative damage approved markers. Our method presents several advantages over traditional methods as it is a direct, non-time-consuming, repeatable, and non-invasive technique that requires only simple pre-treatment of samples without additional reagents and the sample size needed for analysis is small. In principle, each modification of the protein in plasma can be expected to modify its fluorescence properties and hence its lifetime or intensity. The study involved 59 blood donors with no evidence of disease. The research was conducted at excitation wavelengths of 280 nm and 360 nm, and emission was measured at wavelengths of 350 nm and 440 nm, respectively. Our results, although preliminary, suggest that the application of fluorescence measurements can be considered as an effective marker of oxidative stress. Regression analyses showed that a notable growth in fluorescence intensity at 440 nm and a simultaneous decrease in fluorescence intensity and mean fluorescence lifetime at 350 nm are associated with higher levels of oxidative stress., (© 2022. The Author(s).)

The consumption of food for pleasure is mainly associated with adverse health effects. This review was carried out to verify recent reports on the impact of chocolate and wine consumption on cardiovascular health, with a particular focus on atherosclerosis. On one side, these products have proven adverse effects on the cardiovascular system, but on the other hand, if consumed in optimal amounts, they have cardiovascular benefits. The submitted data suggest that the beneficial doses are 30-50 g and 130/250 mL for chocolate and wine, respectively, for women and men. The accumulated evidence indicates that the active ingredients in the products under consideration in this review are phenolic compounds, characterized by anti-inflammatory, antioxidant, and antiplatelet properties. However, there are also some reports of cardioprotective properties of other compounds such as esters, amines, biogenic amines, amino acids, fatty acids, mineral ingredients, and vitamins. Our narrative review has shown that in meta-analyses of intervention studies, consumption of chocolate and wine was positively associated with the beneficial outcomes associated with the cardiovascular system. In contrast, the assessment with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) scale did not confirm this phenomenon. In addition, mechanisms of action of bioactive compounds present in chocolate and wine depend on some factors, such as age, sex, body weight, and the presence of additional medical conditions. Patients using cardiovascular drugs simultaneously with both products should be alert to the risk of pharmacologically relevant interactions during their use. Our narrative review leads to the conclusion that there is abundant evidence to prove the beneficial impact of consuming both products on cardiovascular health, however some evidence still remains controversial. Many authors of studies included in this review postulated that well-designed, longitudinal studies should be performed to determine the effects of these products and their components on atherosclerosis and other CVD (Cardiovascular Disease) disease.

Cardiovascular diseases are the leading cause of mortality worldwide [...].

2-Arylidene-indan-1,3-done derivatives have very different properties, thanks to which they find various applications in science, medicine, and industry. Selected derivatives show antiviral, antibacterial, and anti-inflammatory activity. This paper presents a procedure for the synthesis of a series of indan-1,3-dione derivatives that present antiproliferative activity. The aim of the work was to develop a method of simple synthesis and purification, evaluate the fulfillment of the Lipiński's and Veber's rule, and determine the potential scope of application of the obtained series of compounds. The structure of the synthesized compounds was confirmed, and their lipophilicity was determined using experimental and computational methods. Their antiproliferative activity against selected cell lines was tested in accordance with the MTT protocol; the ability to bind to albumin was tested, and the parameters related to the toxicity of substances in silico were determined. The selected compounds which showed antiproliferative activity were strongly bound to albumin and, in most cases, met the Lipiński's and Veber's rule. Thus, the obtained results suggest that 2-arylidene-indan-1,3-done derivatives appear to be good candidates for drugs with a potential leading structure for further development.

The present review summarizes scientific reports from between 2010 and 2019 on the use of capillary electrophoresis to quantify active constituents (i.e., phenolic compounds, coumarins, protoberberines, curcuminoids, iridoid glycosides, alkaloids, triterpene acids) in medicinal plants and herbal formulations. The present literature review is founded on PRISMA guidelines and selection criteria were formulated on the basis of PICOS (Population, Intervention, Comparison, Outcome, Study type). The scrutiny reveals capillary electrophoresis with ultraviolet detection as the most frequently used capillary electromigration technique for the selective separation and quantification of bioactive compounds. For the purpose of improvement of resolution and sensitivity, other detection methods are used (including mass spectrometry), modifiers to the background electrolyte are introduced and different extraction as well as pre-concentration techniques are employed. In conclusion, capillary electrophoresis is a powerful tool and for given applications it is comparable to high performance liquid chromatography. Short time of execution, high efficiency, versatility in separation modes and low consumption of solvents and sample make capillary electrophoresis an attractive and eco-friendly alternative to more expensive methods for the quality control of drugs or raw plant material without any relevant decrease in sensitivity.

The era of globalization causes that the export and import of food from different continents of the world are becoming more and more common, which may directly contribute to the increase in pollution in them. The presence of mycotoxin in food is an ubiquitous problem. There is very limited information on the possible influence of the composition of herbal mixtures on the presence of mycotoxins in them, which is an area where research can be expanded. The aim of this study was to determine patulin (PAT) in commercial products containing dried elderberry, rose, blueberry, rowan, hawthorn, and chokeberry fruits by enzyme-linked immunosorbent assay technique. Research using this technique allowed for considering the possible influence of the composition of herbal mixtures on the concentration of patulin in them. Patulin was detected in all analyzed samples with wide range of

A new series of hybrid compounds with tropinone and thiazole rings in the structure was designed and synthesized as potential anticancer agents. They were tested against human multiple myeloma (RPMI 8226), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), and mouse skin melanoma (B16-F10) cell lines. Toxicity was tested on human normal skin fibroblasts (HSF) and normal colon fibroblasts (CCD-18Co). The growth inhibition mechanism of the most active derivative was analyzed through investigation of its effect on the distribution of cell cycle phases and ability to induce apoptosis and necrosis in RPMI 8226 and A549 cancer cells. The tyrosinase inhibitory potential was assessed, followed by molecular docking studies. Compounds 3a-3h show high anticancer activity against MDA-MB-231 and B16-F10 cell lines with IC 50 values of 1.51-3.03 µM. Moreover, the cytotoxic activity of the investigated compounds against HSF and CCD-18Co cells was 8-70 times lower than against the cancer cells or no toxicity was shown in our tests, with derivative 3a being particularly successful. The mechanism of action of compound 3a in RPMI 8226 cell was shown to be through induction of cell death through apoptosis. The derivatives show ability to inhibit the tyrosinase activity with a mixed mechanism of inhibition. The final molecular docking results showed for IC 50 distinct correlation with experiment.