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Introduction: Psoriasis is a frequent and incurable skin disease that is an important issue in contemporary dermatology, whereas its pathogenesis is still uncertain. Gasdermin A (GSDMA) is a member of the gasdermin protein family that enables pore formation in cellular membranes leading to cell death called pyroptosis. Objective: Our aim was to investigate the role of GSDMA in psoriatic patients. Method: The study enrolled 60 patients with active plaque-type psoriasis and 30 sex- and age-matched volunteers without dermatoses. GSDMA concentration was assessed in serum and urine samples of all participants using ELISA. GSDMA tissue expression was assessed by immunohistochemistry. Results: GSDMA serum concentration was significantly higher in patients compared to controls, whereas urinary GSDMA/creatinine ratio was insignificantly lower. GSDMA tissue expression was more prominent in psoriatic plaque compared to non-lesional patient skin and healthy skin of subjects without dermatoses. There was a strong negative correlation between GSDMA serum concentration and alanine aminotransferase (ALT) activity. GSDMA did not correlate with PASI or psoriasis duration. Conclusions: Obtained results point to the probable involvement of GSDMA in psoriasis. GSDMA overexpression may probably lead to keratinocytes hyperproliferation and be responsible for triggering inflammation in psoriatic skin. Serum GSDMA, but not urinary GSDMA, could become psoriasis biomarker.

Psoriasis is one of the most common skin diseases and a crucial issue to manage in contemporary dermatology. The search for the details of its pathogenesis, markers and treatment is continuously ongoing. Our aim was to investigate the role of gasdermin B (GSDMB) in psoriasis, the second protein from the gasdermin family, involved in cell death and proliferation. GSDMB serum and urinary concentrations have never been studied in psoriatics, neither tissue expression of GSDMB by immunohistochemistry. The study included 60 psoriatic patients and 30 volunteers without dermatoses as controls. The serum and urinary GSDMB were evaluated by ELISA. Tissue expression of GSDMB was analyzed by immunohistochemistry. The serum and absolute urine concentrations of GSDMB were significantly higher in psoriatic patients than controls without skin diseases (p = 0.0137, p = 0.039 respectively). Urinary GSDMB/creatinine concentration ratio was significantly lower in patients compared to controls (p = 0.0241). The expression of GSDMB in the dermis and epidermis was significantly more prevalent in psoriatic plaque compared to the non-lesional skin and healthy skin of controls (p = 0.0012, p = 0.017, respectively). Serum GSDMB correlated positively with the age of patients (R = 0.41; p = 0.001). Our study adds to the current state of knowledge about psoriasis concerning the potential involvement of GSDMB. Possibly it could be engaged in keratinocytes migration, which requires further research. Elevated serum GSDMB and decreased urinary GSDMB/creatinine concentration ratio could potentially be investigated as psoriasis biomarkers. GSDMB could be investigated in the future as a potential therapeutic target.

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

Background/Aims Intestinal metaplasia (IM) of the stomach is a precancerous condition that is often not visible during conventional endoscopy. Hence, we evaluated the utility of magnification endoscopy and methylene blue (MB) chromoendoscopy to detect IM. Methods We estimated the percentage of gastric mucosa surface staining with MB, mucosal pit pattern, and vessel visibility and correlated it with the presence of IM and the percentage of metaplastic cells in histology, similar to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage. Results IM was found in 25 of 33 (75.8%) patients and in 61 of 135 biopsies (45.2%). IM correlated with positive MB staining (p

Abstract Colorectal cancer (CRC) affects more than 1,000,000 people worldwide each year. Recently, the number of young patients with early-onset colorectal cancer has increased, and right-sided colorectal cancer is still often diagnosed only in advanced stages. The TNM classification is not perfect for CRC staging. This study aimed to perform, for the first time, simultaneous analysis of tumor-infiltrating immune cell density, presence of lymphoid follicles, and budding status in CRC tissue. Intraoperative samples of neoplastic tissue were collected from 195 consecutive patients who were admitted to the surgical ward for elective colorectal surgery. Histological parameters were assessed in the tissue samples: tumor budding foci, poorly differentiated clusters and areas of poorly differentiated components. Tumor-infiltrating immune cells (tumor-associated neutrophils and tumor-infiltrating lymphocytes) were detected in five randomly chosen, areas at the tumor center and at the invasive front. Additionally, the presence of lymphoid follicles in CRC tissue was assessed. Tumor budding parameters were positively correlated with colorectal cancer advancement or histologic (mucinous) type of CRC. The number of poorly differentiated clusters was higher in younger patients. Lower densities of CD3 and CD4 lymphocytes were seen in CRC with a greater depth of tumor invasion. Lower densities of CD3 and CD8 lymphocytes were found in CRC with metastases to the surrounding lymph nodes. The lower density of CD8 lymphocytes was observed in CRC with distant metastases. Lower densities of tumor-associated neutrophils and tumor-infiltrating lymphocytes (CD3 and CD8) were revealed in CRC without lymphoid follicles. The number of lymphoid follicles was higher in patients with less advanced CRCs. Three histopathology markers, such as high tumor budding, scanty lymphocyte infiltration, and the poverty of lymphoid follicles, complement each other, appear to be reliable indicators of colorectal cancer progression, and could be useful in everyday medical practice, but their widespread use requires further research. We propose to take into account these markers, in the assessment of colorectal cancer advancement, in addition to the TNM classification.

Justyna Dorf,1 Konrad Zaręba,2 Joanna Matowicka-Karna,1 Anna Pryczynicz,3 Katarzyna Guzińska-Ustymowicz,3 Anna Zalewska,4 Mateusz Maciejczyk5 1Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland; 2 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bialystok, Poland; 3Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland; 4Independent Laboratory of Experimental Dentistry, Medical University of Bialystok, Bialystok, Poland; 5Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, PolandCorrespondence: Justyna Dorf, Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15a St, Białystok, 15-269, Poland, Tel +48 85 8 31 87 16, Email justyna.dorf@umb.edu.plPurpose: Overproduction of reactive nitrogen species (RNS) causes the nitrosative stress, which plays a vital role in the development of metabolic, inflammatory, and cancerous diseases. However, the role of nitrosative and carbonyl stress in the biology of colorectal cancer (CRC) is still not well understood. Therefore, this study evaluated nitrosative stress, protein and DNA oxidation/glycoxidation, and pro- and anti-inflammatory cytokines in CRC patients compared with healthy controls.Patients and Methods: Fifty-five CRC patients (21 women, 34 men) and 55 healthy controls matched for sex and age were included in the experiment. Nitrosative stress parameters (nitric oxide (NO), peroxynitrite, S-nitrosothiols, and nitrotyrosine), protein oxidation (total thiols) and glycoxidation products (kynurenine N-formylkynurenine, dityrosine, Amadori products, and amyloid), and DNA damage markers (8-hydroxydeoxyguanosine (8-OHdG)), as well as levels of pro- and anti-inflammatory cytokines, were measured in serum or plasma samples.Results: The levels of NO, peroxynitrite, S-nitrosothiols, nitrotyrosine, total thiols, kynurenine, N-formylkynurenine, dityrosine, Amadori product, amyloid, and 8-OHdG, as well as IL1α, IL1β, IL6, IL10, and TNF-α, were significantly higher in CRC patients than in controls. Oxidation and glycoxidation products were positively correlated with pro-inflammatory (IL1α, IL1β, IL6, TNFα) and anti-inflammatory cytokines (IL10), indicating that redox damages may promote inflammation in CRC patients. Many redox biomarkers differentiate patients with CRC from healthy individuals with high sensitivity and specificity.Conclusion: Correlations of chosen oxidative products with pro-inflammatory (IL1α, IL1β, IL6, TNFα) and anti-inflammatory cytokines (IL10) suggest that redox damages may promote inflammation in CRC patients. Thus, our research is the first point for further clinical trials focusing on the evaluation of the diagnostic utility of nitrosative stress biomarkers in a larger group of CRC patients.Graphical Abstract: Keywords: nitrosative stress, cytokines, inflammation, colorectal cancer

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.

Psoriasis is a frequent and incurable skin disease whose pathogenesis is still not fully understood. It is characterized by immune disturbances leading to hyperproliferation and improper differentiation of keratinocytes. Gasdermin E (GSDME) is a protein from the gasdermin family involved in the processes of inflammation and cell death based on apoptosis, necroptosis and pyroptosis. It has never been studied in psoriatics’ sera or urine before. Our study enrolled 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDME concentrations were examined by ELISA and tissue expression of GSDME by immunohistochemistry. Serum GSDME concentration was significantly higher in patients than controls (p < 0.05). There were no differences in urinary GSDME concentrations between patients and controls. GSDME expression was significantly higher in the psoriatic plaque than non-lesional patients’ skin and compared to controls (both p < 0.001). There was no correlation between serum GSDME or its lesional expression and psoriasis severity, age or disease duration. GSDME serum concentration was significantly negatively correlated with BMI, triglycerides and glucose concentrations. The obtained results suggest the engagement of GSDME in psoriasis pathogenesis. It could potentially become a new non-invasive psoriasis marker. Considering its pro-apoptotic influence, GSDME could be compensatively elevated to direct cells towards apoptosis, whereas under other circumstances, it may lead to pyroptosis and sustain inflammation. GSDME may exert a protective influence on the metabolic complications in psoriasis which requires further studies.

Justyna Zi&nacute;czuk,1 Konrad Zar&eogon;ba,2 Joanna Kami&nacute;ska,1 Olga Martyna Koper-Lenkiewicz,1 Violetta Dymicka-Piekarska,1 Anna Pryczynicz,3 Katarzyna Guzi&nacute;ska-Ustymowicz,3 Bogu&lstrok;aw K&eogon;dra,2 Joanna Matowicka-Karna,1 Ma&lstrok;gorzata &Zdot;endzian-Piotrowska,4 Anna Zalewska,5 Mateusz Maciejczyk4 1Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bia&lstrok;ystok, 15-269, Poland; 2 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bia&lstrok;ystok, 15-276, Poland; 3Department of General Pathomorphology, Medical University of Bialystok, Bia&lstrok;ystok, 15-269, Poland; 4Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bia&lstrok;ystok, 15-222, Poland; 5Independent Laboratory of Experimental Dentistry, Medical University of Bialystok, Bia&lstrok;ystok, 15-276, PolandCorrespondence: Justyna Zi&nacute;czukDepartment of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15a St., Bia&lstrok;ystok, 15-269, PolandTel +48 85 8 31 87 16Email justyna.zinczuk@umb.edu.plMateusz MaciejczykDepartment of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Mickiewicza 2c St., Bia&lstrok;ystok, 15-222, PolandTel +48 85 748 55 85Email mat.maciejczyk@gmail.comPurpose: In this study, we evaluated the total antioxidant capacity, nitrosative stress, and protein/DNA oxidation and glycoxidation products in patients with colorectal cancer regarding histopathological parameters associated with the tumour microenvironment, such as inflammatory infiltration and tumour budding and compare all determined parameters between tumours located in the right and left side of the colon and normal mucosa.Patients and Methods: Ferric reducing antioxidant power (FRAP), nitrosative stress (myeloperoxidase (MPO), nitrogen oxide (NO), peroxynitrite, and nitrotyrosine), protein oxidation products (protein carbonyls (PC), total thiols, and ischemia modified albumin (IMA)), protein glycooxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, Amadori product, advanced glycation end products (AGE)) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in homogenates from normal and cancerous tissue of 30 patients with colorectal cancer.Results: Levels of FRAP (p=0.0009), IMA (p=0.0002), kynurenine (p< 0.0001), N-formylkynurenine (p< 0.0001), dityrosine (p< 0.0001), Amadori products (p=0.0024), AGE (p< 0.0001), MPO (p< 0.0001), NO (p< 0.0001) and nitrotyrosine (p=0.0011) were increased, whereas PC (p=0.0004), tryptophan (p< 0.0001), 8-OHdG (p< 0.0001) and peroxynitrite (p=0.0003) were decreased in the left-side tumour compared to the right-side tumour and normal mucosa.Conclusion: Our results showed that colorectal cancer is related with disturbances in antioxidant defense and increased oxidative and nitrosative damages to proteins and DNA. These parameters may be useful for evaluation the progression and differentiation of the tumour location. We also demonstrated that redox indicators may depend on the histological type of the tumour and may influence tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion, inflammatory infiltration, and tumour budding, which are part of the tumour microenvironment.Keywords: oxidative stress, nitrosative stress, redox biomarkers, colorectal cancer

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative–antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures. [ABSTRACT FROM AUTHOR]

Tensins belong to the family of adhesion proteins which form focal adhesions serving as a bridge between the extracellular matrix and intracellular actin skeleton. The tensin family consists of four members (tensin-1 to -4) which are widely expressed in normal and cancerous tissues. The presence of Src homology 2 and phosphotyrosine binding domains is a unique feature of tensins which enables them to interact with tyrosine-phosphorylated proteins in PI3K/Akt and β-integrin/FAK signaling pathways. The tensin-mediated signaling pathway regulates physiological processes including cell motility and cytoskeleton integrity. The expression of tensins varies among cancers. Several papers report tensins as tumor suppressive proteins, whereas tensins may promote epithelial to mesenchymal transition and cancer cell metastasis. Recent findings and further research on tensins as therapeutic targets in cancers may contribute to identifying effective anti-cancer therapy. In this review we focus on the role of tensins in normal and cancer cells. We discuss potential mechanism(s) involved in carcinogenesis.

Tensins belong to the group of adhesion proteins that are involved in cell adhesion and migration, actin cytoskeleton maintenance and intercellular communication. TNS1, TNS2 and TNS3 proteins expression was evaluated in 90 patients with gastric cancer by immunohistochemistry method. TNS1 was more frequently present in non-differentiated tumors compared to poorly and moderately differentiated tumors (p = 0.016). TNS1 was also more often observed in metastatic tumors compared to those without distant metastases (p = 0.001). TNS2 was more common in moderately differentiated tumors than in poorly or non-differentiated ones (p = 0.041). TNS2 expression was also more frequently present in tumors with peritumoral inflammation (p = 0.041) and with concomitant H. pylori infection (p = 0.023). In contrast, TNS3 protein was more prevalent in moderately than in poorly and non-differentiated tumors (p = 0.023). No significant relationship was found between tensins’ expression and the overall survival rate of patients. TNS1 protein expression is associated with a poor-prognosis type of GC. Higher expression of TNS2 is accompanied by peritumoral inflammation and H. pylori infection, which favor the development of GC of a better prognosis, similarly to higher TNS3 protein expression.

Psoriasis is an important disease in dermatological practice and, despite many studies, its pathogenesis is still not fully understood. Gasdermin C (GSDMC; melanoma-derived leucine zipper-containing extranuclear factor, MLZE) is a member of the gasdermin protein family. The study enrolled 60 patients with active plaque-type psoriasis and 30 volunteers without dermatoses. GSDMC concentration was assessed in serum and urine samples of all participants using ELISA. GSDMC tissue expression was assessed by immunohistochemistry. The GSDMC concentration was significantly higher in serum of patients than in controls (p < 0.001). A urinary GSDMC/creatinine ratio was significantly lower in patients than in controls (p < 0.05). Psoriatic lesions exhibited a significantly higher expression of GSDMC than nonlesional patients' skin or controls' skin (p < 0.001 , p < 0.01 , respectively). There was a positive correlation between the GSDMC serum concentration and the age of patients (R = 0.31, p = 0.015) and a negative correlation between GSDMC and RBC (R = −0.37; p = 0.0038), HGB (R = −0.26; p = 0.047), and urea concentration (R = −0.36; p = 0.04). Our study shows the potential involvement of GSDMC in psoriasis. An increased serum GSDMC and a decreased urinary GSDMC/creatinine ratio could be considered noninvasive psoriasis biomarkers, especially of local hypoxia or cell proliferation. [ABSTRACT FROM AUTHOR]

Patients suffering from chronic kidney disease (CKD) are at a 20-fold higher risk of dying due to cardiovascular diseases (CVDs), primarily thrombosis following vascular injury. CKD is connected with retention of uremic toxins, especially indoxyl sulfate (IS), which are currently considered as a non-classical CKD-specific risk factor for CVDs. The present study aimed to examine the effect of chronic exposure to IS on the hemostatic system and arterial thrombosis in a model without greater interferences from the uremic milieu consisting of additional uremic toxins. Forty-eight male Wistar Crl:WI (cmdb) rats were divided into three groups: one control group and two experimental groups, which were exposed to 100 or 200 mg/kg of b.w./day of IS in drinking water for a period of 28 days. The control group received water without IS. At the end of the experiment, the induction of arterial thrombosis was performed. We investigated the impact of IS on thrombosis incidence, kinetics and strength of clot formation, platelet activity, aortic contents of sirtuin (SIRT) 1 and sirtuin 3 (SIRT3), hemostatic system, cardiorespiratory parameters, biochemistry of plasma and urine as well as histology of the thrombus, kidney, and liver. Obtained data revealed that chronic exposure to IS promotes arterial thrombosis via increased levels of complex tissue factor/factor VII, plasminogen activator inhibitor-1 (PAI-1), platelet activation, as well as decreased aortic levels of SIRT1 and SIRT3. Therefore, we hypothesize that IS enhances primary hemostasis leading to augmented formation of platelet plug with increased amounts of fibrin and affects secondary hemostasis through the influence on plasma coagulation and fibrinolysis factors, which results in the increased kinetics and strength of clot formation. The findings described may contribute to a better understanding of the mechanisms leading to increased thrombotic events in patients with CKD with elevated levels of IS.

Tensins belong to the family of adhesion proteins which form focal adhesions serving as a bridge between the extracellular matrix and intracellular actin skeleton. The tensin family consists of four members (tensin-1 to -4) which are widely expressed in normal and cancerous tissues. The presence of Src homology 2 and phosphotyrosine binding domains is a unique feature of tensins which enables them to interact with tyrosine-phosphorylated proteins in PI3K/Akt and β-integrin/FAK signaling pathways. The tensin-mediated signaling pathway regulates physiological processes including cell motility and cytoskeleton integrity. The expression of tensins varies among cancers. Several papers report tensins as tumor suppressive proteins, whereas tensins may promote epithelial to mesenchymal transition and cancer cell metastasis. Recent findings and further research on tensins as therapeutic targets in cancers may contribute to identifying effective anti-cancer therapy. In this review we focus on the role of tensins in normal and cancer cells. We discuss potential mechanism(s) involved in carcinogenesis. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR) as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone structure via AhR pathway. This finding opens new opportunities for the treatment/prevention of osteoporosis in CKD.

This study is the first to assess the diagnostic utility of redox biomarkers in patients with colorectal cancer (CRC). Antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), uric acid (UA), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS), ferric reducing ability (FRAP)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were measured in serum/plasma samples of 50 CRC patients. The activity of SOD was significantly higher whereas the activity of CAT, GPx and GR was considerably lower in CRC patients compared to the control group (p < 0.0001). Levels of UA, TOS, and OSI and concentrations of AGE, AOPP, and MDA were significantly higher, and the levels of GSH, TAC, and FRAP were considerably lower in CRC patients compared to the healthy controls (p < 0.0001). AUC for CAT with respect to presence of lymph node metastasis was 0.7450 (p = 0.0036), whereas AUC for MDA according to the depth of tumour invasion was 0.7457 (p = 0.0118). CRC is associated with enzymatic/non-enzymatic redox imbalance as well as increased oxidative damage to proteins and lipids. Redox biomarkers can be potential diagnostic indicators of CRC advancement.