Novel Properties of Old Propranolol-Assessment of Antiglycation Activity through In Vitro and In Silico Approaches.

Hypertension has earned the "silent killer" nickname since it may lead to a number of comorbidities, including diabetes and cardiovascular diseases. Oxidative stress and protein glycation play vital roles in the pathogenesis of hypertension. Several studies have shown that they profoundly account for vascular dysfunction, endothelial damage, and disruption of blood pressure regulatory mechanisms. Of particular note are advanced glycation end products (AGEs). AGEs alter vascular tissues' functional and mechanical properties by binding to receptors for advanced glycation end products (RAGE), stimulating inflammation and free radical-mediated pathways. Propranolol, a nonselective beta-adrenergic receptor antagonist, is one of the most commonly used drugs to treat hypertension and cardiovascular diseases. Our study is the first to analyze propranolol's effects on protein glycoxidation through in vitro and in silico approaches. Bovine serum albumin (BSA) was utilized to evaluate glycoxidation inhibition by propranolol. Propranolol (1 mM) and BSA (0.09 mM) were incubated with different glycating (0.5 M glucose, fructose, and galactose for 6 days and 2.5 mM glyoxal and methylglyoxal for 12 h) or oxidizing agents (chloramine T for 1 h). Biomarkers of protein glycation (Amadori products (APs), ß-amyloid (ßA), and advanced glycation end products (AGEs)), protein glycoxidation (dityrosine (DT), kynurenine (KYN), and N-formylkynurenine (NFK)), protein oxidation (protein carbonyls (PCs), and advanced oxidation protein products (AOPPs)) were measured by means of colorimetric and fluorimetric methods. The scavenging of reactive oxygen species (hydrogen peroxide, hydroxyl radical, and nitric oxide) and the antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating (FIC) assays)) of propranolol were also evaluated. Additionally, in silico docking was performed to showcase propranolol's interaction with BSA, glycosides, and AGE/RAGE pathway proteins. The products of protein glycation (↓APs, ↓ßA, ↓AGEs), glycoxidation (↓DT, ↓KYN, ↓NFK), and oxidation (↓PCs, ↓AOPPs) prominently decreased in the BSA samples with both glycating/oxidizing factors and propranolol. The antiglycoxidant properties of propranolol were similar to those of aminoguanidine, a known protein oxidation inhibitor, and captopril, which is an established antioxidant. Propranolol showed a potent antioxidant activity in the FIC and H2O2 scavenging assays, comparable to aminoguanidine and captopril. In silico analysis indicated propranolol's antiglycative properties during its interaction with BSA, glycosidases, and AGE/RAGE pathway proteins. Our results confirm that propranolol may decrease protein oxidation and glycoxidation in vitro. Additional studies on human and animal models are vital for in vivo verification of propranolol's antiglycation activity, as this discovery might hold the key to the prevention of diabetic complications among cardiology-burdened patients.

Associations of oxidative stress, metabolic disorders in colorectal cancer patients.

Introduction: Colorectal cancer have been one of the most common malignant neoplasm in the world. In most patients with this cancer, we can observe both redox homeostasis and nutritional disorders. Aim: To assess the occurrence of oxidative stress in patients with colorectal cancer and its severity depending on the nutritional status of patients. Material and methods: The study group consisted of 50 patients with colorectal cancer. In the control group, samples were obtained from 40 healthy subjects. Basal metabolic index and nutrition risk screening (NRS) 2002 scale was completed. The total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) were determined yielding the oxidative stress index (OSI) determined by the TOS/TAC ratio and TAC/MDA ratio. Results: There were statistically significant differences (p < 0.05) in the levels of not only TAC, TOS, OSI, but also MDA and TAC/MDA. In healthy patients, the TAC and TAC/MDA level was significantly higher (p < 0.05) compared to the cancer patients, while the TOS, OSI and MDA level was significantly lower (p < 0.05). In patients with BMI < 24.9 kg/m2, the level of TAC was significantly higher and the level of TOS was significantly lower (p < 0.05) compared to patients with BMI > 24.9 kg/m2. In patients with features of malnutrition according to the NRS 2002 scale, TOS and OSI were statistically significantly higher (p < 0.05). Conclusions: Neoplastic disease, such as colorectal cancer, precipitates an increase in oxidative stress. Concurrently, the nutritional status of patients, especially malnutrition, further intensifies this process.

Comparison of smoking traditional, heat not burn and electronic cigarettes on salivary cytokine, chemokine and growth factor profile in healthy young adults-pilot study.

Objective: Smoking is the cause of numerous oral pathologies. The aim of the study was to evaluate the effect of smoking traditional cigarettes, e-cigarettes, and heat-not-burn products on the content of salivary cytokines, chemokines, and growth factors in healthy young adults. Design: Three groups of twenty-five smokers each as well as a control group matched in terms of age, gender, and oral status were enrolled in the study. In unstimulated saliva collected from study groups and participants from the control group, the concentrations of cytokines, chemokines, and growth factors were assessed by Bio-Plex® Multiplex System. Results: We demonstrated that smoking traditional cigarettes is responsible for increasing the level of IFN-γ compared to non-smokers and new smoking devices users in unstimulated saliva in the initial period of addiction. Furthermore, e-cigarettes and heat-not-burn products appear to have a similar mechanism of affecting the immune response system of unstimulated saliva, leading to inhibition of the local inflammatory response in the oral cavity. Conclusion: Smoking traditional cigarettes as well as e-cigarettes and heat-not-burn products is responsible for changes of the local immune response in saliva. Further research is necessary to fill the gap in knowledge on the effect of new smoking devices on the oral cavity immune system.

Oxidative stress parameters in women and men with suicidal thoughts and following a suicide attempt.

Background: This study aimed to evaluate oxidative stress parameters in individuals with depression and schizophrenia, considering gender differences, and manifesting suicidal behavior, encompassing thoughts without a tendency to be realized, thoughts with a tendency to be realized, and suicide attempts. Methods: From among the patients from Department of Psychiatry 120 individuals were selected who met the inclusion criteria and did not meet the exclusion criteria for the study. In the initial phase of the project, patients eligible for the study underwent the M.I.N.I 7.0.2 questionnaire (Mini International Neuropsychiatric Interview). Subsequently, in the second phase of the research, venous blood samples were collected from the patients for the purpose of conducting biochemical assessments, focusing on oxidative stress parameters. Results: The obtained results suggest that redox biomarkers, namely TOS (total oxidation state) and OSI (TOS/TAC ratio), in the blood plasma of women increase in tandem with the severity of suicidal behavior. No notable alterations in SOD (Cu-Zn-superoxide dismutase), GPx (glutathione peroxidase), and GSH (reduced glutathione) concentrations and activity were noted between groups exhibiting suicidal behavior. The observed variations in the concentrations and activity of antioxidant parameters were significant solely in comparison to the control group. Conclusions: Redox biomarkers TOS and OSI could prove valuable in diagnosing women at a genuine risk of committing suicide. On the other hand, antioxidant parameters - SOD, GPx, and GSH may be instrumental in identifying patients with suicidal behaviors, without specifying their intensity.

Redox Biomarkers - An Effective Tool for Diagnosing COVID-19 Patients and Convalescents.

Aim: COVID-19 triggers the overproduction of reactive oxygen species (ROS) which, in combination with a weakened antioxidant barrier, can lead to protein oxidation and lipid peroxidation. The aim of this study was to evaluate enzymatic and non-enzymatic antioxidants, the overall redox potential, and protein and lipid peroxidation products in COVID-19 patients, convalescents, and healthy subjects, and to the determine the diagnostic applicability of these parameters in COVID-19 patients. Materials and Methods: The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects who were selected for the research based on age and sex. The study was conducted between 20 February 2021 and 20 November 2021 in Bialystok, Poland. The antioxidant barrier, redox status, and oxidative damage products were assessed in serum/plasma samples with the use of colorimetric and spectrophotometric assays. Results: Glutathione reductase (GR) activity was higher, whereas total antioxidant capacity (TAC) was lower in COVID-19 patients than in convalescents (p<0.0001) and the control group (p<0.0001). The concentrations of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were higher in COVID-19 patients (p<0.0001) and convalescents (p<0.0001) than in the control group. AGEs were the most effective diagnostic biomarker for differentiating COVID-19 patients from the control group (AUC=0.9971) and convalescents from the control group (AUC=1.000). Conclusion: An infection with the SARS-CoV-2 disrupts the redox balance and increases protein oxidation and lipid peroxidation. AGEs fulfill the criteria for a potential diagnostic biomarker in COVID-19 patients and convalescents.

Revealing novel biomarkers for diagnosing chronic kidney disease in pediatric patients.

Pediatric chronic kidney disease (CKD) is a clinical condition characterized by progressive renal function deterioration. CKD diagnosis is based on glomerular filtration rate, but its reliability is limited, especially at the early stages. New potential biomarkers (citrulline (CIT), symmetric dimethylarginine (SDMA), S-adenosylmethionine (SAM), n-butyrylcarnitine (nC4), cis-4-decenoylcarnitine, sphingosine-1-phosphate and bilirubin) in addition to creatinine (CNN) have been proposed for early diagnosis. To verify the clinical value of these biomarkers we performed a comprehensive targeted metabolomics study on a representative cohort of CKD and healthy pediatric patients. Sixty-seven children with CKD and forty-five healthy children have been enrolled in the study. Targeted metabolomics based on liquid chromatography-triple quadrupole mass spectrometry has been used for serum and plasma samples analysis. Univariate data analysis showed statistically significant differences (p < 0.05) in the concentration of CNN, CIT, SDMA, and nC4 among healthy and CKD pediatric patients. The predictive ability of the proposed biomarkers was also confirmed through specificity and sensitivity expressed in Receiver Operating Characteristic curves (AUC = 0.909). In the group of early CKD pediatric patients, AUC of 0.831 was obtained, improving the diagnostic reliability of CNN alone. Moreover, the models built on combined CIT, nC4, SDMA, and CNN allowed to distinguish CKD patients from healthy control regardless of blood matrix type (serum or plasma). Our data demonstrate potential biomarkers in the diagnosis of early CKD stages.

The antiglycation potential of H1 receptor antagonists - in vitro studies in bovine serum albumin model and in silico molecular docking analyses.

The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.

Significance of nitrosative stress and glycoxidation products in the diagnosis of COVID-19.

Nitrosative stress promotes protein glycoxidation, and both processes can occur during an infection with the SARS-CoV-2 virus. Therefore, the aim of this study was to assess selected nitrosative stress parameters and protein glycoxidation products in COVID-19 patients and convalescents relative to healthy subjects, including in reference to the severity of COVID-19 symptoms. The diagnostic utility of nitrosative stress and protein glycoxidation biomarkers was also evaluated in COVID-19 patients. The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects. Nitrosative stress parameters (NO, S-nitrosothiols, nitrotyrosine) and protein glycoxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, AGEs) were measured in the blood plasma or serum with the use of colorimetric/fluorometric methods. The levels of NO (p = 0.0480), S-nitrosothiols (p = 0.0004), nitrotyrosine (p = 0.0175), kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan fluorescence was significantly (p < 0.0001) lower in COVID-19 patients than in the control group. Significant differences in the analyzed parameters were observed in different stages of COVID-19. In turn, the concentrations of kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan levels were significantly (p < 0.0001) lower in convalescents than in healthy controls. The ROC analysis revealed that protein glycoxidation products can be useful for diagnosing infections with the SARS-CoV-2 virus because they differentiate COVID-19 patients (KN: sensitivity-91.20%, specificity-92.00%; NFK: sensitivity-92.37%, specificity-92.00%; AGEs: sensitivity-99,02%, specificity-100%) and convalescents (KN: sensitivity-82.22%, specificity-84.00%; NFK: sensitivity-82,86%, specificity-86,00%; DT: sensitivity-100%, specificity-100%; AGE: sensitivity-100%, specificity-100%) from healthy subjects with high sensitivity and specificity. Nitrosative stress and protein glycoxidation are intensified both during and after an infection with the SARS-CoV-2 virus. The levels of redox biomarkers fluctuate in different stages of the disease. Circulating biomarkers of nitrosative stress/protein glycoxidation have potential diagnostic utility in both COVID-19 patients and convalescents.

Can smoking alter salivary homeostasis? A systematic review on the effects of traditional and electronic cigarettes on qualitative and quantitative saliva parameters.

The available literature indicates that smoking causes quantitative and qualitative changes in saliva. However, there is a lack of studies summarizing the knowledge in this area, and there are no clear guidelines on the use of salivary biomarkers for assessing exposure to cigarette smoke (CS). The present work aimed to provide a systematic review of the literature regarding the influence of smoking traditional and electronic cigarettes, as well as heat-not-burn products, on salivary homeostasis. An electronic search of the literature from 1982 to 2023 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Based on the inclusion criteria, 65 studies were used for the final review. Smoking traditional as well as electronic cigarettes negatively affects salivary biomarkers, including the salivary flow rate, pH, antibody titer, electrolyte concentration, microflora composition, redox balance, and inflammation, in terms of both quantity and quality. However, to date, only single salivary biomarkers have been compared in traditional and electronic cigarette smokers. It can be concluded that the salivary production rate, pH, microbiome, and cytokines can be used to assess exposure to CS smoke. There is a lack of convincing evidence to compare the toxic influence of traditional and electronic cigarettes on salivary homeostasis. Future experiments should include long-term randomized clinical trials on larger populations of smokers.

Urinary Concentration of Renal Biomarkers in Healthy Term Neonates: Gender Differences in GST-pi Excretion.

BACKGROUND Serum creatinine, the criterion standard in assessment of renal function, is not reliable for the neonatal period because of its dependence on renal immaturity and maternal creatinine levels. Thus, it is important to study other biomarkers of renal function in neonates. The present study aimed to measure the urinary concentration of renal biomarkers: calbindin, clusterin, GST-pi (glutathione-S-transferase-alpha), KIM-1 (kidney injury molecule 1), MCP-1 (monocyte chemoattractant protein-1), and B2M (beta 2-microglobulin) in healthy term neonates. MATERIAL AND METHODS In the study, we included 80 healthy term neonates - 40 females and 40 males. We collected the neonates' urine on their first day of life. Urinary concentrations of calbindin, clusterin, KIM-1, MCP-1, and B2M were assessed using an immunoassay for kidney toxicology research. Because dilution of the urine affects the concentrations of urinary biomarkers, we normalized them to the concentration of urinary creatinine (Cr) and present them as biomarker/Cr ratios. RESULTS We obtained the following values of the assessed biomarker/Cr ratios (median [Q1-Q3]): calbindin/Cr.: 197.04 (56.25-595.17), KIM-1/Cr: 0.09 (0.04-0.18), MCP-1/Cr: 0.05 (0.02-0.14), B2M/Cr: 126.12 (19.03-342.48), GST-pi/Cr in boys: 1.28 (0.46-3.77), GST-pi/Cr in girls: 8.66 (2.51-27.82), clusterin/Cr: 4.55 (1.79-12.97) ng/mg Cr. CONCLUSIONS We showed the urinary levels of calbindin, clusterin, GST-pi, KIM-1, MCP-1, B2M in white, West Slavic, healthy term neonates. We found that in there is an association between female sex and a higher urinary GST-pi excretion, but urinary excretion of calbindin, clusterin, KIM-1, MCP-1, and B2M is sex-independent. The urinary levels of the assessed biomarkers do not depend on the method of delivery.

Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer.

Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.

The preliminary study suggests an association between NF-ĸB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients.

The significant role of increased activation of 20S proteasomes in the development of abdominal aortic aneurysms has been well-established in a mouse model. The available literature lacks similar studies concerning brain aneurysms. The aim of the study was to verify the hypothesis that patients with unruptured intracranial aneurysms (UIA) have increased 20S proteasome ChT-L activity compared to the control group of individuals without vascular lesions in the brain. In the next step, the relationship between the activity of 20S proteasomes ChT-L and precursor proteins from the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family, namely NF-κB1 (p105), NF-κB2 (p100), NF-κB p65, and the inflammatory chemokine MCP-1, was examined. Patients with UIA had significantly higher 20S ChT-L proteasome activity compared to the control group. Patients with multiple aneurysms had significantly higher 20S proteasome ChT-L activity compared to those with single aneurysms. In patients with UIA, the activity of the 20S proteasome ChT-L negatively correlated with the concentration of NF-κB1 (p105) and NF-κB p65 precursor proteins and positively correlated with the concentration of the cerebrospinal fluid chemokine MCP-1. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-κB pathway.

Impact of Smoking on Salivary Lipid Profile and Oxidative Stress in Young Adults: A Comparative Analysis between Traditional Cigarettes, E-Cigarettes, and Heat-Not-Burn Products.

BACKGROUND Smoking nicotine is considered to be one of the most harmful addictions, leading to the development of a number of health complications, including many pathologies in the oral cavity. The aim of this study was to examine the effect of smoking traditional cigarettes, e-cigarettes, and heat-not-burn products on profiles of salivary lipids and lipid peroxidation products in the unstimulated and stimulated saliva of healthy young adults with a smoking habit of up to 3 years. MATERIAL AND METHODS We enrolled 3 groups of 25 smoking patients each and a control group matched for age, gender, and oral status. In saliva collected from patients from the study groups and participants from the control group, the concentrations of sphingolipids: sphingosine, sphinganine, sphingosine-1-phosphate, ceramides, and salivary lipid peroxidation products - malondialdehyde (MDA) and 4-hydroxynonenal (HNE) - were measured. The normality of distribution was assessed using the Shapiro-Wilk test. For comparison of the results, one-way analysis of variance (ANOVA) followed by post hoc Tukey test was used. RESULTS We demonstrated that each type of smoking causes a decrease in the concentration of salivary lipids, and there was an increased concentration of salivary MDA and 4-HNE. CONCLUSIONS Smoking in the initial period of addiction leads to an increase in the concentration of lipid peroxidation products through increased oxidative stress, leading to disturbance of the lipid balance of the oral cavity (eg, due to damage to cell membranes).

Preliminary evaluation of the antiglycoxidant activity of verapamil using various in vitro and in silico biochemical/biophysical methods.

Introduction: Glycoxidative stress is essential for linking glucose disturbances and cardiovascular diseases. Unfortunately, contemporary antidiabetic drugs do not have an antiglycative effect but only lower blood glucose levels. Therefore, there is an intense search for substances that could inhibit protein glycation and prevent diabetic complications. A potential antioxidant activity has been demonstrated with verapamil, a phenylalkylamine derivative belonging to selective calcium channel blockers. Verapamil has a well-established position in cardiology due to its wide range of indications and good safety profile. Nevertheless, the antidiabetic activity of verapamil is still unclear. We are the first to comprehensively evaluate the verapamil's effect on protein glycoxidation using various in vitro and in silico models. Methods: Bovine serum albumin (BSA) was used to assess the rate of glycoxidation inhibition by verapamil. As glycating factors, sugars (glucose, fructose, and ribose) and aldehyde (glyoxal) were used. Chloramine T was used as an oxidizing agent. Aminoguanidine (protein glycation inhibitor) and Trolox (antioxidant) were used as control substances. The biomarkers of oxidation (total thiols, protein carbonyls, advanced oxidation protein products), glycation (Amadori products, ß-amyloid, advanced glycation end products [AGEs]), and glycoxidation (tryptophan, kynurenine, N-formylkynurenine, dityrosine) were evaluated using colorimetric and fluorimetric methods. The mechanism of antiglycative activity of verapamil was assessed using in silico docking to study its interaction with BSA, glycosidases, and seventeen AGE pathway proteins. Results: In all in vitro models, biomarkers of protein glycation, oxidation, and glycoxidation were significantly ameliorated under the influence of verapamil. The glycoxidation inhibition rate by verapamil is comparable to that of potent antiglycating agents and antioxidants. The molecular docking simulations showed that verapamil bound preferentially to amino acids prone to glycoxidative damage out of an α-glucosidase's active center. Among all AGE pathway proteins, verapamil was best docked with the Janus kinase 2 (JAK2) and nuclear factor-κB (NF-κB). Discussion: The results of our study confirm the antiglycoxidant properties of verapamil. The drug's action is comparable to recognized substances protecting against oxidative and glycation modifications. Verapamil may be particularly helpful in patients with cardiovascular disease and concomitant diabetes. Studies in animal models and humans are needed to confirm verapamil's antiglycative/antidiabetic activity.

Association of Ischemia-Modified Albumin (IMA) in Saliva, Serum, and Urine with Diagnosis of Chronic Kidney Disease (CKD) in Children: A Case-Control Study.

BACKGROUND Ischemia-modified albumin (IMA) is a secreted biomarker for ischemic oxidative stress. This case-control study aimed to evaluate the association of ischemia-modified albumin (IMA) in saliva, serum, and urine with diagnosis of chronic kidney disease (CKD) in 24 children. MATERIAL AND METHODS The study involved 24 children with CKD. CKD was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic criteria. The control group consisted of 24 healthy children who were matched for age and gender to the experimental group. The concentration of IMA was determined by the colorimetric method in non-stimulated whole saliva (NWS), stimulated whole saliva (SWS), serum, and urine of children with CKD. The Mann-Whitney U test was used for inter-group comparisons. RESULTS IMA levels were significantly higher in NWS (P=0.0082) and SWS (P=0.0014) of children with CKD than in the control group. The concentration of IMA in NWS was correlated with standard indicators of kidney function, including the estimated glomerular filtration rate (r=-0.798, P≤0.0001), stage of CKD (r=0.814, P≤0.0001), and serum creatinine (r=0.711, P≤0.0001) and urea levels (r=0.738, P≤0.0001). CONCLUSIONS Salivary IMA concentration depends on renal function in children. Salivary IMA discriminates children with end-stage kidney disease from children with mild and moderate CKD and healthy children with high sensitivity and specificity. Further research is required, including assessment of the diagnostic usefulness and validation of the biomarker in a clinical diagnostic study.

Unveiling COVID-19 Secrets: Harnessing Cytokines as Powerful Biomarkers for Diagnosis and Predicting Severity.

Introduction: In coronavirus disease (COVID-19), inflammation takes center stage, with a cascade of cytokines released, contributing to both inflammation and lung damage. The objective of this study is to identify biomarkers for diagnosing and predicting the severity of COVID-19. Materials and Methods: Cytokine levels were determined in the serum from venous blood samples collected from 100 patients with COVID-19 and 50 healthy controls. COVID-19 patients classified based on the Modified Early Warning (MEWS) score. Cytokine concentrations were determined with a multiplex ELISA kit (Bio-Plex Pro™ Human Cytokine Screening Panel). Results: The concentrations of all analyzed cytokines were elevated in the serum of COVID-19 patients relative to the control group, but no significant differences were observed in interleukin-9 (IL-9) and IL-12 p70 levels. In addition, the concentrations of IL-1α, IL-1ß, IL-1ra, IL-2Rα, IL-6, IL-12 p40, IL-18, and tumor necrosis factor alpha (TNFα) were significantly higher in symptomatic patients with accompanying pneumonia without respiratory failure (stage 2) than in asymptomatic/mildly symptomatic patients (stage 1). Conclusion: The study revealed that IL-1ra, IL-2Rα, IL-6, IL-8, IL-12 p40, IL-16, and IL-18 levels serve as potential diagnostic biomarkers in COVID-19 patients. Furthermore, elevated IL-1α levels proved to be valuable in assessing the severity of COVID-19.

The Effect of Antidepressant Treatment on Neurocognitive Functions, Redox and Inflammatory Parameters in the Context of COVID-19.

Inflammation is an important component of the etiopathology of depression that uses oxidative and nitrosative stress (O&NS) and elevated inflammatory markers. SARS-CoV-2 infection is also associated with abnormal inflammatory processes, which may impair effective treatment of depression in COVID-19 survivors. In the presented study, thirty-three hospitalized patients with major depressive disorder (MDD) were started on antidepressant treatment, and twenty-one were re-evaluated after 4-6 weeks. The control group consisted of thirty healthy volunteers. All participants underwent neuropsychiatric evaluation, biochemical blood and urine analyses. The results of the research demonstrated positive correlations of the Hamilton Depression Rating Scale (HAM-D) scores with serum catalase (CAT) and urinary S-Nitrosothiols levels, and the Beck Depression Inventory (BDI) scores with serum reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Depressed patients with a history of COVID-19 prior to the treatment had higher urinary nitric oxide (NO) levels and lower serum glutathione peroxidase (GPx) levels. In the control group, COVID-19 survivors had higher levels of urinary N-formylkynurenine (NFK). Our results suggest that the antidepressant treatment has a modulating effect on O&NS, reduces depressive symptoms and improves cognitive functions The present study does not indicate that clinical response to antidepressant treatment is associated with COVID-19 history and baseline SARS-CoV-2 antibody levels. Nevertheless, further research in this area is needed to systematize antidepressant treatment in COVID-19 survivors.

Preliminary Assessment of Polysaccharide-Based Emulgels Containing Delta-Aminolevulinic Acid for Oral Lichen planus Treatment.

Photodynamic therapy using delta-aminolevulinic acid is considered a promising option in the treatment of oral lichen planus. In the present work, three emulgel compositions prepared from natural polysaccharide gums, tragacanth, xanthan and gellan, were preliminarily tested for oromucosal delivery of delta-aminolevulinic acid. Apart from cytotoxicity studies in two gingival cell lines, the precise goal was to investigate whether the presence of the drug altered the rheological and mucoadhesive behavior of applied gelling agents and to examine how dilution with saliva fluid influenced the retention of the designed emulgels by oromucosal tissue. Ex vivo mucoadhesive studies revealed that a combination of xanthan and gellan gum enhanced carrier retention by buccal tissue even upon dilution with the saliva. In turn, the incorporation of delta-aminolevulinic acid favored interactions with mucosal tissue, particularly formulations comprised of tragacanth. The designed preparations had no significant impact on the cell viability after a 24 h incubation in the tested concentration range. Cytotoxicity studies demonstrated that tragacanth-based and gellan/xanthan-based emulgels might exert a protective effect on the metabolic activity of human gingival fibroblasts and keratinocytes. Overall, the presented data show the potential of designed emulgels as oromucosal platforms for delta-aminolevulinic acid delivery.

The usefulness of a complete blood count in the prediction of the first episode of schizophrenia diagnosis and its relationship with oxidative stress.

A complete blood count (CBC) is a routinely performed blood examination. Only a few studies assess the relationship between CBC and oxidative stress (OS) in schizophrenia (SZ). The aim of the study was to assess the utility of CBC in the prediction of SZ diagnosis, and the relationship between CBC and OS. The study included: 47 individuals with the first episode of psychosis (26 drug-naive: FEP-nt; 21 patients under antipsychotic treatment: FEP-t) and 30 healthy persons (control group, HC). CBC and oxidative stress-related parameters were assessed in blood samples. The FEP group had higher levels of WBC, MCHC, NEU, MONO, EOZ, BASO, and %EOZ compared to HC (p<0.05). Various relationships between OS and CBC were found, and this connection was significantly different between healthy individuals and patients. The most promising C&RT model for discriminating FEP from HC was combining monocytes, eosinophils, and neutrophils (accuracy: 77%, 95%CI = 0.67-0.87). The analysis singled out WBC and HT (accuracy: 74%, 95%CI = 0.64-0.90) as the most promising to distinguish FEP-nt from HC; WBC and %Neu to allocate to FEP-t or HC group (accuracy: 87%, 95%CI = 0.64-0.90); RDW-SD and LYMPH (accuracy: 86%, 95% CI = 0.75-97) for distinguishing FEP-nt from FEP-t. CBC could be a promising, cheap tool to determine abnormalities related to schizophrenia. However, more studies with larger sample sizes are required.

The Urinary Concentrations of Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and Osteopontin in the Healthy Term and Stable Preterm Neonates: A Pilot Study.

BACKGROUND: In neonates, the assessment of kidney function with serum creatinine is limited; therefore, more effective biomarkers are needed. AIM: The study aimed at analyzing the concentrations of renal biomarkers (osteopontin, cystatin C, and NGAL) in neonates. MATERIAL AND METHODS: The study included 80 term and 20 preterm neonates aged 28-33 weeks of gestation. Biomarkers were measured in urine. Term neonates' urine was collected on the 1st day of life. Preterm neonates' urine was collected on the 1st, 8th, 15th, 22nd day of life. Biomarkers' concentrations were normalized to urinary creatinine (cr.) and presented as urinary biomarker/cr. ratios. RESULTS: Median values of biomarker/creatine ratios in term and preterm neonates were the following: cystatin C/cr.: 7.26 and 439.49; osteopontin/cr.: 135.86 and 1633.37; NGAL/cr. in girls: 212.14 and 256.93; and NGAL/cr. in boys 27.123 and 65.29 ng/mg cr. In preterm neonates the cystatin C/cr. ratio was higher on the 1st than on the 8th day. The osteopontin/cr. ratio did not differ between the days. The NGAL/cr. ratio in girls was higher on the 8th than on the 22nd day, and in boys, the lowest was on the 22nd day. CONCLUSIONS: Prematurity in stable, Caucasian neonates might cause higher osteopontin and cystatin C excretion, but not NGAL. The excretion of NGAL and cystatin C, but not osteopontin, may change during first weeks of premature neonate's life.