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Abstract The study assessed selected parameters of redox status in the plasma of patients suffering from high myopia (HM). Thirty-five children with mean age 13.7 ± 2.7 years with HM and 40 healthy children were included. Plasma redox status parameters were determined using colorimetric kits. The levels of retinol, α-tocopherol and coenzyme Q10 were determined with a high-performance liquid chromatograph. Negative correlations were observed between the concentrations of retinol and the axial length of the eye (r = − 0.514 p 26 mm compared to controls were established. Significantly lower retinol and α-tocopherol concentrations were found in patients with the axial length of the eye > 26 mm compared to those with the axial length of the eye ≤ 26 mm (p

Abstract 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

Abstract 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

Disturbances in pro/antioxidant balance emerge as a crucial element in bipolar disorder (BD). Some studies suggest that treatment effects on trace element concentration in BD. This study aimed to identify (a) the changes related to oxidative stress in BD and their relationship with trace elements engaged in pro/antioxidant homeostasis; (b) BD biomarkers using machine learning algorithm classification and regression tree (C&RT) analysis. 62 individuals with BD and 40 healthy individuals (HC) were included in the study. The concentration of pro/antioxidant state and concentration of selenium, zinc, arsenic in blood were assessed. We found a higher concentration of total antioxidant capacity, catalase, advanced oxidation protein products and a lower concentration of 4-hydroxynonenal (4-HNE), glutathione, glutathione peroxidase (GPx) in BD compared to HC. All examined trace elements were lower in the BD group compared to HC. A combination of two variables, 4-HNE (cut-off: ≤ 0.004 uM/mg protein) and GPx (cut-off: ≤ 0.485 U/mg protein), was the most promising markers for separating the BD from the HC. The area under the receiver operating characteristic curve values for C&RT was 90.5%. Disturbances in the pro/antioxidant state and concentration of trace elements of patients with BD may be a target for new therapeutic or diagnostic opportunity of BD biomarkers.

Abstract 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.

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.

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.

BackgroundThis 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.MethodsFrom 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.ResultsThe 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.ConclusionsRedox 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.

An important drug used in the treatment of Parkinson’s disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.

AimThe aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients’ MEWS scores was also assessed.Materials and methodsThe serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system.ResultsThe study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-β, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity.ConclusionsMIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.

AbstractBackground This study aimed to evaluate the redox status, antioxidant barrier, and oxidative damage to proteins, lipids, and DNA in patients with gastric cancer (GC). We are also the first to assess the diagnostic utility of redox parameters in patients with GC with respect to histopathological parameters.Methods Fifty patients with gastric cancer and 50 healthy controls matched for sex and age were included in the study. The antioxidant barrier, redox status, and oxidative damage products were measured in serum/plasma samples using colorimetric or spectrophotometric methods.Results The activity of superoxide dismutase – SOD (p

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, β-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.

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.

BackgroundNitrosative stress leads to protein glycoxidation, but both processes may be strongly related to the cancer development. Therefore, the aim of this study was to assess the nitrosative stress and protein glycoxidation products in patients with gastric cancer in comparison with healthy controls. We are also the first to evaluate the diagnostic utility of nitrosative stress and protein glycoxidation markers in gastric cancer patients in respect to histopathological classifications (TNM, Lauren’s and Goseki’s classification) and histopathological parameters such as histological type, histological differentiation grade, presence of vascular or neural invasion, desmoplasia and Helicobacter pylori infection.MethodsThe study included 50 patients with gastric cancer and 50 healthy controls matched for sex and age. Nitrosative stress parameters and protein glycoxidation products were measured colorimetrically/fluorometrically in plasma or serum samples. Student’s t-test or Mann-Whitney U-test were used for statistical analysis.ResultsNO, S-nitrosothiols, nitrotyrosine, kynurenine, N-formylkynurenine, dityrosine, AGE and Amadori products were significantly increased whereas tryptophan fluorescence was decreased in patients with gastric cancer compared to the healthy control. Nitrosative stress and glycoxidation products may be useful in diagnosis of gastric cancer because they differentiate patients with gastric cancer from healthy individuals with high sensitivity and specificity. Some of the determined parameters are characterised by high AUC value in differentiation of GC patients according to the histopathological parameters.ConclusionsGastric cancer is associated with enhanced circulating nitrosative stress and protein glycation. Although further research on a tissue model is needed, plasma/serum biomarkers may be dependent on tumour size, histological type, tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion and Helicobacter pylori infection. Thus, circulating biomarkers of nitrosative stress/protein glycoxidation may have potential diagnostic significance in gastric cancer patients.

IntroductionAgomelatine is an atypical antidepressant drug enhancing norepinephrine and dopamine liberation; nevertheless, additional mechanisms are considered for the drug's pharmacological action. Since protein glycoxidation plays a crucial role in depression pathogenesis, agomelatine's impact on carbonyl/oxidative stress was the research purpose.MethodsReactive oxygen species scavenging (hydroxyl radical, hydrogen peroxide, and nitrogen oxide) and antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating assays) of agomelatine were marked. Agomelatine's antiglycoxidation properties were assayed in sugars (glucose, fructose, and galactose) and aldehydes- (glyoxal and methylglyoxal) glycated bovine serum albumin (BSA). Aminoguanidine and α-lipoic acid were used as standard glycation/oxidation inhibitors.ResultsAgomelatine did not show meaningful scavenging/antioxidant capacity vs. standards. Sugars/aldehydes increased glycation (↑kynurenine, ↑N-formylkynurenine, ↑dityrosine, ↑advanced glycation end products, and ↑β-amyloid) and oxidation (↑protein carbonyls and ↑advanced oxidation protein products) parameters in addition to BSA. Standards restored BSA baselines of glycation and oxidation markers, unlike agomelatine which sometimes even intensifies glycation above BSA + glycators levels. Molecular docking analysis of agomelatine in BSA demonstrated its very weak binding affinity.DiscussionAgomelatine's very low affinity to the BSA could proclaim non-specific bonding and simplify attachment of glycation factors. Thereby, the drug may stimulate brain adaptation to carbonyl/oxidative stress as the systematic review indicates. Moreover, the drug's active metabolites could exert an antiglycoxidative effect.

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.

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.

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.

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

Background: Histamine H2 receptor antagonists are a group of drugs that inhibit gastric juice secretion in gastrointestinal diseases. However, there is evidence to suggest that H2 blockers have a broader spectrum of activity. The antioxidant properties of H2 blockers have not been fully elucidated, and their anti-glycation potential has not been studied to date. Therefore, this is the first study to compare the antioxidant and antiglycation potentials of the most popular H2 antagonists (ranitidine, cimetidine, and famotidine) on protein glycoxidation in vitro. Methods: Bovine serum albumin (BSA) was glycated using sugars (glucose, fructose, galactose, and ribose) as well as aldehydes (glyoxal and methylglyoxal). Results: In the analyzed group of drugs, ranitidine was the only H2 blocker that significantly inhibited BSA glycation in all tested models. The contents of protein carbonyls, protein glycoxidation products (↓dityrosine, ↓N-formylkynurenine), and early (↓Amadori products) and late-stage (↓AGEs) protein glycation products decreased in samples of glycated BSA with the addition of ranitidine relative to BSA with the addition of the glycating agents. The anti-glycation potential of ranitidine was comparable to those of aminoguanidine and Trolox. In the molecular docking analysis, ranitidine was characterized by the lowest binding energy for BSA sites and could compete with protein amino groups for the addition of carbonyl groups. H2 blockers also scavenge free radicals. The strongest antioxidant properties are found in ranitidine, which additionally has the ability to bind transition metal ions. The systematic literature review also revealed that the anti-glycation effects of ranitidine could be attributed to its antioxidant properties. Conclusions: Ranitidine showed anti-glycation and antioxidant properties. Further research is needed, particularly in patients with diseases that promote protein glycation.

Despite the high biocompatibility of titanium and its alloys, the need to remove titanium implants is increasingly being debated due to the potential for adverse effects associated with long-term retention. Therefore, new solutions are being sought to enhance the biocompatibility of titanium implants. One of them is to increase the thickness of the passive layer of the implant made of titanium dioxide. We were the first to evaluate the effect of hard-anodized (type II) Ti-6Al-4V alloy discs on the cytotoxicity, mitochondrial function, and redox balance of fibroblasts mitochondria compared to standard-anodized (type III) and non-anodized discs. The study used fibroblasts obtained from human gingival tissue. The test discs were applied to the bottom of 12-well plates. Cells were cultured for 24 h and 7, 14, and 21 days and mitochondria were isolated. We demonstrated the occurrence of oxidative stress in the mitochondria of fibroblasts of all tested groups, regardless of the presence and type of anodization. Type II anodization prevented changes in complex II activity (vs. control). The lowest degree of citrate synthase inhibition occurred in mitochondria exposed to titanium discs with type II anodization. In the last phase of culture, the presence of type II anodization reduced the degree of cytochrome c oxidase inhibition compared to the other tests groups and the control group, and prevented apoptosis. Throughout the experiment, the release of titanium, aluminium, and vanadium ions from titanium discs with a hard-anodized passive layer was higher than from the other titanium discs, but decreased with time. The obtained results proved the existence of dysfunction and redox imbalance in the mitochondria of fibroblasts exposed to hard-anodized titanium discs, suggesting the need to search for new materials perhaps biodegradable in tissues of the human body.

Background: Distinguishing between a pathologic state and renal development is important in neonatology. Because the assessment of serum creatinine in neonates is not reliable, better biomarkers are needed. Trefoil factor 3 (TFF3) is proposed as a biomarker of kidney injury. The study aimed to assess its urinary concentration in healthy term and stable preterm neonates. Material and methods: The study included 80 term and 20 preterm neonates born in the Department of Perinatology of the University Clinical Hospital in Bialystok. Urine was obtained from the term neonates on the 1st day of life and from the preterm neonates on the 1st, 8th, 15th and 22nd day of life. The urinary concentration of TFF3 was determined using a commercially available immunoassay and was normalized for the urinary creatinine concentration (cr.). Results: The values of TFF3/cr. were higher in the preterm than in the term neonates (p < 0.05) (median (Q1–Q3): 1486.85 (614.92–3559.18) and 317.29 (68.07–671.40) ng/mg cr.). They did not differ in the subsequent days of the preterm neonates’ lives. The ROC curve for TFF3/cr. in the preterm and term neonates showed AUC = 0.751 (cut-off value = 1684.25 ng/mg cr.). Conclusions: Prematurity is associated with higher urinary excretion of TFF3. Male gender is associated with an increased urinary TFF3 excretion in term neonates.

Abstract Alzheimer’s disease (AD) is associated with the deposition of β-amyloid in the brain. AD accounts for over 50% of cases of dementia which results from disturbances in redox homeostasis. Indeed, increased intensity of protein oxidation and nitration as well as lipid peroxidation is observed in brain areas with considerable amounts of amyloid plaques and neurofibrillary tangles. However, little is known about the oxidoreductive balance of salivary glands in AD patients. Therefore, the aim of this study was to evaluate the antioxidant barrier and oxidative/nitrosative stress biomarkers in stimulated saliva and blood of AD patients. The study was participated by 25 AD patients and 25 non-demented controls without neurological diseases or cognitive impairment, matched by age and gender to the study group. The number of patients was determined based on a previous pilot study (test power = 0.9). We found a significant decrease in the activity of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), increased activity of catalase (CAT) and reduced concentration of plasma non-enzymatic antioxidants (uric acid, UA and reduced glutathione, GSH). In contrast, in the stimulated saliva of AD patients we observed significantly decreased activity of all antioxidant enzymes (SOD, CAT and GPx) as well as concentration of GSH compared to the control group. The content of lipid (malondialdehyde, MDA) and protein (advanced oxidation protein products, AOPP; advanced glycation end-products, AGE) oxidation products as well as biomarkers of nitrosative stress (peroxynitrite, nitrotyrosine) was significantly higher in both saliva and plasma of AD patients compared to the controls. In AD patients, we also observed a considerable decrease in stimulated saliva secretion and salivary total protein content, and an increase in salivary β-amyloid concentration. In conclusion, AD results in redox imbalance towards oxidative reactions, both at the level of the oral cavity and the entire body. General redox balance disturbances do not coincide with salivary redox balance disturbances. Reduction in stimulated saliva secretion in AD patients reflects secretory dysfunction of the parotid glands.

Heart failure (HF) is one of the leading causes of death worldwide. HF results not only in cardiovascular dysfunction, but also numerous pathologies in the oral cavity and salivary glands. The present study is the first to evaluate whether salivary inflammatory and anti-inflammatory factors may be related with the occurrence of hyposalivation in HF patients. We also evaluated the potential of salivary biomarkers in the diagnostics of HF. The study included 30 women with HF and 30 sex- and age-matched healthy controls. We demonstrated significantly higher levels of pro-inflammatory cytokines, anti-inflammatory cytokines, Th1, Th2, Th17, chemokines and growth factors in unstimulated saliva of HF patients compared to controls. However, the results do not indicate dominance of either branch of the immune response. The concentration of selected biomarkers is significantly higher in patients with HF and salivary gland dysfunction compared to patients with normal saliva secretion and healthy subjects (IL-1β, TNF-α, IL-7, IL-13, INF-γ, IL-12, IL-15, IL-5, IL-6, IL-9, IL-17, MCP-1/CCL-2, EOTAXIN/CCL11, RANTES/CCL5, GM-CSF, VEGF, FGF basic, PDFG-BB). Multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors is highly dependent on salivary gland function, i.e. salivary flow rate, total protein content and amylase activity. Using receiver operating characteristic (ROC) analysis, we showed that salivary TNF-α, INF-γ, IL-12 and EOTAXIN/CCL11 differentiated patients with HF and hyposalivation with the highest sensitivity and specificity compared to patients with normal salivary secretion and controls. Interestingly, the content of some pro- and anti-inflammatory mediators in saliva significantly exceeds their concentration in plasma. In addition, salivary biomarker levels do not reflect their plasma content, which may suggest a different nature/severity of inflammatory changes at the central (blood) and local (salivary) levels. Although our study was purely observational, the significantly higher concentration of inflammatory parameters in saliva compared to plasma, as well as the lack of saliva-blood correlation, may suggest increased production/secretion of these compounds in salivary cells of HF patients. ROC analysis did not confirm the diagnostic utility of salivary cytokines and chemokines in the differential diagnosis of HF patients.

Abstract Inflammation plays a crucial role in stroke pathogenesis. Thus, it is not surprising that cytokines, chemokines, and growth factors have been advocated in stroke diagnostics. Our study is the first to evaluate the salivary cytokine profile in patients with ischemic stroke. Twenty-five patients with subacute ischemic stroke and an age-, sex-, and oral hygiene status-matched control group were enrolled in the study. The number of patients was set a priori based on our previous experiment (α = 0.05, test power = 0.9). Salivary concentrations of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) were assessed using an ELISA method. We showed that salivary TNF-α and IL-6 were significantly higher, whereas IL-10 content was statistically lower in both non-stimulated (NWS) and stimulated (SWS) whole saliva of ischemic stroke patients. However, evaluation of cytokines in NWS rather than in SWS may be of greater diagnostic value. Of particular note is salivary TNF-α, which may indicate cognitive/physical impairment in post-stroke individuals. This parameter distinguishes stroke patients from healthy controls and correlates with cognitive decline and severity of functional impairment. It also differentiates (with high sensitivity and specificity) stroke patients with normal cognition from mild to moderate cognitive impairment. Saliva may be an alternative to blood for assessing cytokines in stroke patients, although further studies on a larger patient population are needed.

The aim of the study was to assess the total antioxidant/oxidant status in the plasma and urine of patients with adrenal tumors. The study group consisted of 60 patients (31 women and 29 men) with adrenal masses, classified into three subgroups: non-functional incidentaloma, pheochromocytoma and Cushing’s/Conn’s adenoma. The number of patients was set a priori based on our previous experiment (α = 0.05, test power = 0.9). Antioxidant activity (Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Oxidative Stress Index (OSI)) and antiradical activity (Radical-Scavenging Activity Assay (DPPH), Ferric-Reducing Antioxidant Power (FRAP)) were measured using colorimetric methods. FRAP level was decreased in plasma and urine incidentaloma (p

Stroke is one of the most common cerebrovascular diseases. Despite significant progress in understanding stroke pathogenesis, cases are still increasing. Thus, laboratory biomarkers of stroke are sought to allow rapid and non-invasive diagnostics. Ischemia-reperfusion injury is an inflammatory process with characteristic cellular changes leading to microvascular disruption. Several studies have shown that hyperactivation of xanthine oxidase (XO) is a major pathogenic factor contributing to brain dysfunction. Given the critical role of XO in stroke complications, this study aimed to evaluate the activity of the enzyme and its metabolic products in the saliva of stroke subjects. Thirty patients in the subacute phase of stroke were included in the study: 15 with hemorrhagic stroke and 15 with ischemic stroke. The control group consisted of 30 healthy subjects similar to the cerebral stroke patients regarding age, gender, and status of the periodontium, dentition, and oral hygiene. The number of individuals was determined a priori based on our previous experiment (power of the test = 0.8; α = 0.05). The study material was mixed non‐stimulated whole saliva (NWS) and stimulated saliva (SWS). We showed that activity, specific activity, and XO output were significantly higher in NWS of ischemic stroke patients than in hemorrhagic stroke and healthy controls. Hydrogen peroxide and uric acid levels were also considerably higher in NWS of ischemic stroke patients. Using receiver operating curve (ROC) analysis, we demonstrated that XO-specific activity in NWS distinguishes ischemic stroke from hemorrhagic stroke (AUC: 0.764) and controls (AUC: 0.973) with very high sensitivity and specificity. Saliva collection is stress-free, requires no specialized medical personnel, and allows continuous monitoring of the patient’s condition through non-invasive sampling multiple times per day. Salivary XO also differentiates with high accuracy (100%) and specificity (93.75%) between stroke patients with mild to moderate cognitive decline (AUC = 0.988). Thus, salivary XO assessment may be a potential screening tool for a comprehensive neuropsychological evaluation. To summarize, our study demonstrates the potential utility of salivary XO in the differential diagnosis of stroke.

Background. Finding the associations between schizophrenia symptoms and the biomarkers of inflammation, oxidative stress and the kynurenine pathway may lead to the individualization of treatment and increase its effectiveness. Methods. The study group included 82 schizophrenia inpatients. The Positive and Negative Symptoms Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS) and the Calgary Depression in Schizophrenia Scale were used for symptom evaluation. Biochemical analyses included oxidative stress parameters and brain-derived neurotrophic factor (BDNF). Results. Linear models revealed the following: (1) malondiadehyde (MDA), N-formylkynurenine (N-formKYN), advanced oxidation protein products (AOPP), advanced glycation end-products of proteins (AGE) and total oxidative status (TOS) levels are related to the PANSS-total score; (2) MDA, reduced glutathione (GSH) and BDNF levels are related to the PANSS-negative score; (3) TOS and kynurenine (KYN) levels are related to the PANSS-positive score; (4) levels of total antioxidant status (TAS) and AOPP along with the CDSS score are related to the BACS-total score; (5) TAS and N-formKYN levels are related to the BACS-working memory score. Conclusions. Oxidative stress biomarkers may be associated with the severity of schizophrenia symptoms in positive, negative and cognitive dimensions. The identification of biochemical markers associated with the specific symptom clusters may increase the understanding of biochemical profiles in schizophrenia patients.

Depression (MDD) is a leading psychiatric entity worldwide, with a high impact on individual life and public health. In recent years, efforts have been made to elucidate its biological underpinnings. MDD biomarker research provides promise for a better understanding of the biochemical processes involved in its pathogenesis. Oxidative and nitrosative stress (O&NS) and lipid disturbances are reported as major factors favoring the occurrence of depression. A total of 29 patients with MDD and 30 healthy volunteers were examined using the Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), and the Beck Depression Inventory (BDI). Blood and urine were collected to search for potential MDD biomarkers. O&NS parameters and β-amyloid were assessed in the urine, while cholesterol fractions were assessed in the blood. The group of depressed patients was characterized by higher concentrations of urine superoxide dismutase (SOD), 3-nitrotyrosine (3-NT), catalase (CAT), reduced glutathione (GSH), tryptophan (TRY), and serum triglycerides (TGA), along with lower levels of serum high-density lipoprotein (HDL). Elevated urine 3-NT and decreased serum HDL, considered together, were found to have the greatest potential as markers of depression. The study supports the importance of oxidative stress and cholesterol disturbances in MDD. Further research is required to assess their clinical usefulness as markers.

Alcohol abuse as well as smoking cigarettes has been proven to negatively affect the oral environment. The aim of this work was to provide a systematic review of the literature on the influence of ethanol and cigarette smoking on oral redox homeostasis. A search was performed for scientific articles indexed in the PubMed, Medline and Web of Science databases. We identified 32,300 articles, of which 54 were used for the final review, including the results from 2000 to 2021. Among the publications used to write this article, n = 14 were related to the influence of alcohol consumption (clinical studies n = 6, experimental studies n = 8) and n = 40 were related to the influence of smoking (clinical studies n = 33, experimental studies n = 7) on oral redox homeostasis. The reviewed literature indicates that alcohol abusers and smokers are more likely to suffer from salivary gland dysfunction, as well as develop precancerous lesions due to DNA damage. Compared to alcohol abstainers and non-smokers, alcohol drinkers and smokers are also characterized by a deterioration in periodontal health measured by various indicators of periodontal status. In summary, alcohol abuse and smoking are associated with disrupted oral redox homeostasis, which may lead not only to tooth loss, but also contribute to various adverse effects related to mental health, digestive processes and chronic inflammation throughout the human body.

Pro/antioxidant imbalance has been reported in schizophrenia (SZ). However, the results of studies are inconsistent and usually do not include other factors that are highly affected by oxidative stress (OS).This cross-sectional study aimed to determine the serum levels of OS markers and their potential connection with schizophrenia. The total sample comprised 147: 98 individuals with SZ −47 first-episode (FS) and 49 chronic patients (CS)—and 49 healthy individuals (HC) as a control group. The examination included clinical variables and serum levels of antioxidants and oxidative damage products. The significant changes were observed in concentrations of all examined markers, without any specific direction of the pro/antioxidant balance shift between SZ and HC. In the regression model adjusted for cofounders, catalase: OR = 0.81 (95%CI: 0.74–0.88); glutathione peroxidase: OR = 1.06 (95%CI: 1.02–1.10); total antioxidant capacity: OR = 0.85 (95%CI: 0.75–0.98); oxidative stress index: OR = 1.25 (95%CI: 1.03–1.52); ferric reducing ability of plasma: OR = 0.79 (95%CI: 0.69–0.89); advanced glycation end products: OR = 1.03 (95%CI: 1.01–1.04); and advanced oxidation protein products (AOPP): OR = 1.05 (95%CI: 1.03–1.07) turned out to be significant predictors of schizophrenia. In the multiple stepwise regression model, pro/antioxidant status and their interaction with the duration of illness-related factors affected schizophrenia symptoms: positive symptoms (FRAPxKYN), negative (DITYR, FRAP, CAT), general (KYN), and over-all psychopathology (KYNxNFK). The results confirm differences in serum levels of oxidative biomarkers between SZ patients and healthy individuals. The pro/antioxidant status could be considered a predictor of schizophrenia and the factor affects patients' symptom severity.

The treatment of diabetes mellitus aftermaths became one of medicine's most significant therapeutical and financial issues in the XXI century. Most of which are related to protein glycation and oxidative stress caused by long lasting periods of hyperglycemia. Thus, even within a venerable one, searching for new drugs, displaying anti-glycation and anti-oxidative properties seem useful as an additive therapy of diabetes. In this paper, we assessed the anti-glycating properties of phloroglucinol, a drug discovered in the XIX century and still used in many countries for its antispasmodic action. Herewith, we present its effect on protein glycation, glycoxidation, and oxidative damage in an albumin glycation/oxidation model and HepG2 cells treated with high glucose concentrations. The phloroglucinol showed the strongest and the widest protective effect within all analyzed antiglycating (aminoguanidine, pioglitazone) and anti-oxidative (vitamin C, GSH) agents. To the very best of our knowledge, this is the first study showing the properties of phloroglucinol in vitro what once is proven in other models might deepen its clinical applications.

Trastuzumab is indicated in the adjuvant setting for the early and intermediate stages of breast cancer (BC) positive for epidermal growth factor receptor 2 (HER2). Although HER2 in BC patients tends to disrupt pro-oxidant and inflammatory signaling, the influence of trastuzumab in modulating this process remains unknown. Due to the absence of any chemotherapeutic or chemoprophylactic agents for trastuzumab-induced side effects, this study investigated the potential role of regular physical exercise in modulating the antioxidant defenses, oxidative stress, and nitrosative damage in BC patients during trastuzumab treatment. Aim: The study aimed to analyze the relationship between regular physical activity and the redox status in women with BC during trastuzumab therapy. Materials and methods: We observed 50 BC patients during trastuzumab therapy in two groups: one that undertook moderately intensive supervised physical exercises, and a second that performed physical activity according to the recommendations for cancer patients, along with a third (control) group of healthy women. Results: The antioxidant enzyme and non-enzymatic antioxidant activities were significantly higher in the exercised group compared with the other participants. The concentrations of lipid and protein oxidative damage and nitrosative stress products were significantly higher in both BC groups than in the healthy controls. Conclusions: Trastuzumab treatment stimulates a redox response in BC patients. The results highlight the oxidative imbalance in parallel with regular physical training in women with BC during trastuzumab therapy. Further studies are needed to analyze different intensities and levels of physical training in women with BC during trastuzumab treatment.

The toxic properties of ethanol are inextricably linked to oxidative stress. Despite many reports on the effects of alcohol dependence on blood redox homeostasis, there are no data on the oxidative stress profile in alcohol-poisoned cases. There are also no data on the diagnostic usefulness of redox biomarkers determined post-mortem in various biological fluids. This work investigates the utility of enzymatic and non-enzymatic antioxidant barrier, redox status, and oxidative/nitrosative stress biomarkers in different biological fluids (such as blood, urine, vitreous humor, and cerebrospinal fluid) in the post-mortem study of patients with acute alcohol intoxication. The study group included those who died due to acute ethanol intoxication (n = 22). The research showed a significant increase in glutathione peroxidase activity, total antioxidant status, ferric reducing antioxidant power, and tryptophan concentration only in the study group’s urine compared to the control. In other circulating fluids, both antioxidant enzyme activities and glycoxidation product concentrations were not significantly different in individuals who died of alcohol overdose compared with those who died suddenly. We also did not observe a connection between oxidation–reduction balance and the amount of alcohol consumed before death. These unexpected observations may be caused by irreversible post-mortem changes occurring at the cellular level due to autolysis and putrefaction. In summary, the use of circulating body fluids to assess redox homeostasis is limited in the post-mortem analysis. Our results indicate the increased stability of urine collected post mortem compared to other circulating bioliquids. Further studies are needed to assess the intensity of oxidative and carbonyl stress in ethanol-damaged organs and the effects of post-mortem processes on cellular redox balance.

Introduction: The diagnosis and treatment of dementia is one of the greatest challenges in contemporary health care. The widespread use of dementia biomarkers would improve the quality of life of patients and reduce the economic costs of the disease. The aim of the study was to evaluate the usefulness of proteins related to the Alzheimer's disease pathogenesis—amyloid beta isoform (Aβ) and total tau protein (t-tau), as well as the quite recently discovered marker YKL-40 in the most common types of dementia.Methods: 60 dementia (AD—Alzheimer's disease, VaD—vascular dementia, MxD—mixed dementia) and 20 cognitively normal subjects over 60 years old were examined. Subjects with dementia of etiology different than AD or VaD and with neoplastic or chronic inflammatory diseases were excluded. Concentrations of Aβ40, Aβ42, t-tau, and YKL-40 were measured in serum using ELISA kits on admission and after 4 weeks of inpatient treatment. ANOVA and Tukey's test or Dunn's test were used to perform comparison tests between groups. Correlations were measured using Pearson's coefficient. Biomarker diagnostic utility was assessed with ROC analysis.Results: YKL-40 differentiates between cognitively normal and mild dementia patients with 85% sensitivity and specificity and t-tau with 72% sensitivity and 70% specificity. YKL-40 and t-tau concentrations correlate with each other and with the severity of clinically observed cognitive decline.Conclusions: YKL-40 is a sensitive and specific biomarker of early dementia and, to a lesser extent, of dementia progression, however, many comorbidities may influence its levels. In such conditions, less specific but still reliable t-tau may serve as an alternative marker. Obtained results did not confirm the diagnostic utility of amyloid biomarkers.

Despite high biocompatibility of titanium and its alloys, this metal causes various side effects in the human body. It is believed that titanium biomaterials may induce an innate/adaptive immune response. However, still little is known about changes caused by titanium mandible implants, particularly with regard to bone healing. The latest studies showed disturbances in the antioxidant barrier, increased oxidative/nitrosative stress, as well as mitochondrial abnormalities in the periosteum covering titanium mandible fixations; nevertheless, the impact of titanium implants on free radical production, inflammation, and mandible apoptosis are still unknown. Because severe inflammation and apoptosis are among the main factors responsible for disturbances in osteointegration as well as implant rejection, this study is the first to evaluate pro-oxidant enzymes, cytokines as well as pro- and anti-apoptotic proteins in the periosteum of patients with a broken jaw, treated with titanium miniplates and miniscrews. The study group consisted of 29 patients with double-sided fracture of the mandible body requiring surgical treatment. We found significantly higher activity of NADPH oxidase and xanthine oxidase as well as enhanced rate of free radical production in the periosteum of patients in the study group compared to the control group. The markers of inflammation [interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β) and β-glucuronidase (GLU)] as well as apoptosis [Bax, Bax/Bcl-2 ratio, caspase-3 (CAS-3) and nitric oxide (NO)] were significantly elevated in periosteum covering titanium fixations compared to the control group. In the study group, we also demonstrated an increased content of titanium on the periosteum surface, which positively correlated with CAS-3 activity. The study led us to the conclusion that titanium mandible implants increase the production of pro-inflammatory cytokines, and enhance free radical generation in the periosteum covering titanium miniplates and miniscrews. Additionally, exposure to Ti6Al4V titanium alloy induces apoptosis in the mandible periosteum. However, no clinical signs of the said phenomena have been observed.

To allow better diagnosis and management of psychiatric illnesses, the use of easily accessible biomarkers are proposed. Therefore, recognition of some diseases by a set of related pathogenesis biomarkers is a promising approach. The study aims to assess the usefulness of examining oxidative stress (OS) in schizophrenia as a potential biomarker of illness using the commonly used data mining decision tree method. The study group was comprised of 147 participants: 98 patients with schizophrenia (SZ group), and the control group (n = 49; HC). The patients with schizophrenia were divided into two groups: first-episode schizophrenia (n = 49; FS) and chronic schizophrenia (n = 49; CS). The assessment included the following biomarkers in sera of patients: catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase-1 (SOD-1), glutathione reductase (GR), reduced glutathione (GSH), total antioxidant capacity (TAC), ferric reducing ability of plasma (FRAP), advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), dityrosine (DITYR), kynurenine (KYN), N-formylkynurenine (NFK), tryptophan (TRY), total oxidant status (TOS), nitric oxide (NO) and total protein. Maximum accuracy (89.36%) for distinguishing SZ from HC was attained with TOS and GPx (cut-off points: 392.70 and 15.33). For differentiating between FS and CS, the most promising were KYN, AOPP, TAC and NO (100%; cut-off points: 721.20, 0.55, 64.76 and 2.59). To distinguish FS from HC, maximum accuracy was found for GSH and TOS (100%; cut-off points: 859.96 and 0.31), and in order to distinguish CS from HC, the most promising were GSH and TOS (100%; cut-off points: 0.26 and 343.28). Using redox biomarkers would be the most promising approach for discriminating patients with schizophrenia from healthy individuals and, in the future, could be used as an add-on marker to diagnose and/or respond to treatment.

Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with good retentivity at the mucosa intended for the therapy of oromucosal conditions, especially infectious diseases. Multilayer films composed of layers of oppositely charged polymers separated by ionically interacting polymeric chains creating polyelectrolyte complexes represent very interesting and relatively poorly explored area. We aimed to develop the antifungal multilayer systems composed of cationic chitosan and anionic pectin as potential platforms for controlled delivery of clotrimazole. The systems were pharmaceutically characterized with regard to inter alia their release kinetics under different pH conditions, physicomechanical, or mucoadhesion properties with using an animal model of the buccal mucosa. The antifungal activity against selected Candida sp. and potential cytotoxicity with regard to human gingival fibroblasts were also evaluated. Interactions between polyions were characterized with Fourier transform infrared spectroscopy. Different clotrimazole distribution in the films layers highly affected their in vitro dissolution profile. The designed films were recognized as intelligent pH-responsive systems with strong antifungal effect and satisfactory safety profile. As addition of chitosan resulted in the improved antifungal behavior of the drug, the potential utilization of the films in resistant cases of oral candidiasis might be worth of further exploration.

Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model. Keywords: Ataxia-telangiectasia (A-T), Bloom syndrome (BS), Nijmegen breakage syndrome (NBS), Oxidative stress, Oxidative damage, Antioxidants

Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated in vitro and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the in vivo phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Twenty two Caucasian children with AT and twelve patients with NBS were studied. Enzymatic and non-enzymatic antioxidants – glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase-1 (SOD) and uric acid (UA); redox status—total antioxidant capacity (TAC) and ferric reducing ability of plasma (FRAP); and oxidative damage products−8-hydroxy-2′-deoxyguanosine (8-OHdG), advanced glycation end products (AGE), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE) protein adducts, and 8-isoprostanes (8-isop) were evaluated in serum or plasma samples. We showed that CAT, SOD and UA were significantly increased, while TAC and FRAP levels were statistically lower in the plasma of AT patients compared to controls. In NBS patients, only CAT activity was significantly elevated, while TAC was significantly decreased as compared to healthy children. We also showed higher oxidative damage to DNA (↑8-OHdG), proteins (↑AGE, ↑AOPP), and lipids (↑4-HNE, ↑8-isop) in both AT and NBS patients. Interestingly, we did not demonstrate any significant differences in the antioxidant defense and oxidative damage between AT and NBS patients. However, in AT children, we showed a positive correlation between 8-OHdG and the α-fetoprotein level as well as a negative correlation between 8-OHdG and IgA. In NBS, AGE was positively correlated with IgM and negatively with the IgG level. Summarizing, we demonstrated an imbalance in cellular redox homeostasis and higher oxidative damage in AT and NBS patients. Despite an increase in the activity/concentration of some antioxidants, the total antioxidant capacity is overwhelmed in children with AT and NBS and predisposes them to more considerable oxidative damage. Oxidative stress may play a major role in AT and NBS phenotype.

The study’s aim was a clinical observation concerning the influence of oral health on functional status in stroke patients undergoing neurorehabilitation. This pilot cross-sectional clinical study was performed in 60 subacute phase stroke patients during 12 weeks of treatment. The program was patient-specific and consisted of neurodevelopmental treatment by a comprehensive rehabilitation team. The functional assessment was performed using the Barthel index (BI), Berg balance scale (BBS), functional independence measure (FIM), and Addenbrooke’s cognitive examination III (ACE III) scales. Oral health was assessed according to World Health Organization (WHO) criteria, and it was presented using DMFT, DMFS, gingival index (GI), and plaque index (PlI). Significant improvement in many functional scales was noticed. However, important differences in most dental parameters without relevant changes in GI and PlI after the study were not observed. Reverse interdependence (p < 0.05) was shown between physical functioning (BI, FIM, or BBS) with GI and PlI results, and most dental parameters correlated with ACE III. Using multivariate regression analysis, we showed that ACE III and BI are predictive variables for DMFT, just as FIM is for DS (p < 0.05). The present research revealed that poor oral health status in patients after stroke might be associated with inpatient rehabilitation results.

Chronic heart failure (HF) is an important clinical, social, and economic problem. A key role in HF progression is played by oxidative stress. Free oxygen radicals, formed under the conditions of hypoxia and reperfusion, participate in myocardial stunning and other forms of post-reperfusion damage. HF patients also suffer from disorders connected with saliva secretion. However, still little is known about the mechanisms that impair the secretory function of salivary glands in these patients. In the presented study, we were the first to compare the antioxidant barrier, protein glycoxidation, and nitrosative/nitrative stress in non-stimulated (non-stimulated whole saliva (NWS)) and stimulated (SWS) saliva of HF patients. The study included 50 HF patients with normal saliva (NS) secretion (n = 27) and hyposalivation (HS) (n = 23), as well as an age- and gender-matched control group (n = 50). We demonstrated that, in NWS of HF patients with HS, the concentration of low-molecular-weight non-enzymatic antioxidants decreased (↓total polyphenols, ↓ascorbic acid, ↓reduced glutathione, ↓albumin) compared to HF patients with normal saliva (NS) secretion, as well as the control group (except albumin). We also observed increased content of protein glycoxidation products (↑dityrosine, ↑kynurenine, ↑glycophore) in NWS and SWS of HF patients with HS compared to healthy controls. Interestingly, the content of dityrosine, N-formylkynurenine, and glycophore in NWS was also significantly higher in HF patients with HS compared to those with NS secretion. The concentration of NO was considerably lower, while the levels of peroxynitrite and nitrotyrosine were significantly higher in NWS and SWS of HF subjects with HS compared to the controls. Salivary gland dysfunction occurs in patients with chronic HF with the submandibular salivary glands being the least efficient. Oxidative/nitrosative stress may be one of the mechanisms responsible for the impairment of salivary gland secretory function in HF patients.

Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers.