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

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

Serum Clusterin Concentration and Its Glycosylation Changes as Potential New Diagnostic Markers of SARS-CoV-2 Infection and Recovery Process.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Glycoprotein clusterin (CLU) has many functions such as phagocyte recruitment, complement system inhibition, apoptosis inhibition, hormone and lipid transport, as well as in the immune response. The study aimed to assess the changes in CLU concentrations and the profile and degree of CLU glycosylation between patients with severe COVID-19, convalescents, and healthy subjects (control). The profile and degree of serum CLU N-glycosylation were analyzed using lectin-ELISA with specific lectins. CLU concentrations were significantly lower and relative reactivities of CLU glycans with SNA (Sambucus nigra agglutinin) were significantly higher in severe COVID-19 patients in comparison to convalescents and the control group. The relative reactivities of CLU glycans with MAA (Maackia amurensis agglutinin), together with relative reactivity with LCA (Lens culinaris agglutinin), were also significantly higher in patients with severe COVID-19 than in convalescents and the control group, but they also significantly differed between convalescents and control. The development of acute inflammation in the course of severe COVID-19 is associated with a decrease in CLU concentration, accompanied by an increase in the expression of α2,3-linked sialic acid, and core fucose. Both of these parameters can be included as useful glycomarkers differentiating patients with severe COVID-19 from convalescents and the control group, as well as convalescents and healthy subjects.

Are Changes in Serum IgG Glycosylation Related to the Severe Course of SARS-CoV-2 Infection and Recovery Process? In Search of New Diagnostic and Prognostic Biomarkers.

Introduction: Immunoglobulin G (IgG) glycosylation affects its effector functions and is essential in many steps of the inflammatory cascade. Therefore, it may be an important parameter for assessing the body's immune response during the course of COVID-19 (Coronavirus disease 2019). Methods: The N- and O-glycosylation of serum IgG in severe COVID-19 patients (n=87), convalescents (n=50), and healthy subjects (n=65) were examined using a modified lectin-ELISA method with specific biotinylated lectins. The obtained data were analyzed using STATISTICA 13.3PL software. Results: We showed significantly higher expression of Lewisx oligosaccharide structures in severe COVID-19 patients than in the other two groups. Moreover, significantly lower expression of Lewisy sugar structures in IgG glycans was observed in the convalescents when compared with COVID-19 patients and healthy subjects. The lowest expression of highly branched N-glycans in cases of severe COVID-19 indicates that the development of the disease is associated with the presence of typical IgG biantennary N-glycans. The lack of significant differences in the expression of Tn antigen in IgG between studied groups and the significantly lower expression of T antigen in convalescents compared to the patients with severe COVID-19 and healthy subjects indicates a decrease in the content of the T antigen in IgG O-glycans in subjects recovered from COVID-19. Substantially higher reactivities of IgG O-glycans with Jacalin observed in COVID-19 patients and convalescents in comparison to the control group were most probably caused by increased expression of core 3 O-glycans in IgG. Conclusion: Severe COVID-19 is accompanied by the expression in serum IgG of sialylated biantennary and highly branched N-glycans, decorated by fucose of Lewisx and Lewisy structures. The higher reactivity of IgG O-glycans with Jacalin in severe COVID-19 patients and convalescents indicates that the disease development and the recovery process are most probably accompanied by increased expression of the core 3 O-glycans.

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

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

New Insights on the Progesterone (P4) and PGRMC1/NENF Complex Interactions in Colorectal Cancer Progression.

The literature data regarding the risk of colorectal cancer (CRC) in the context of hormone therapy (HT), including both estrogen-progestogen combinations and estrogen alone, are inconclusive. The precise relationship underlying the action of progesterone (P4) and progesterone receptors in CRC has yet to be determined. We characterized the expression profiles of both nuclear and membrane progesterone receptors and their potential cofactors in CRC tissues. Additionally, we analyzed the P4 and NENF treatment effects on the cell proliferation and invasion of DLD-1 and HT-29 colorectal cancer cells. We observed a weak expression of the nuclear P4 receptor (PGR), but an abundant expression of the P4 receptor membrane component 1 (PGRMC1) and neuron-derived neurotrophic factor (NENF) in the CRC tissues. P4 treatment stimulated the proliferation of the DLD-1 and HT-29 CRC cells. The co-treatment of P4 and NENF significantly increased the invasiveness of the DLD-1 and HT-29 cells. A functional analysis revealed that these effects were dependent on PGRMC1. AN immunocytochemical analysis demonstrated a cytoplasmic co-localization of PGRMC1 and NENF in the CRC cells. Moreover, the concentration of serum NENF was significantly higher in CRC patients, and P4 treatment significantly increased the release of NENF in the DLD-1 cells. P4 or NENF treatment also significantly increased the IL-8 release in the DLD-1 cells. Our data may provide novel insights into the action of P4 and PGRMC1/NENF in CRC progression, where NENF may act as a potential PGRMC1 co-activator in non-classical P4 signaling. Furthermore, NENF, as a secreted protein, potentially could serve as a promising circulating biomarker candidate for distinguishing between colorectal cancer patients and healthy individuals, although large-scale extensive studies are needed to establish this.

Neutrophil/Lymphocyte Ratio (NLR) and Lymphocyte/Monocyte Ratio (LMR) - Risk of Death Inflammatory Biomarkers in Patients with COVID-19.

Aim: The aim of our retrospective study was search for new prognostic parameters, which can help quickly and cheaply identify patients with risk for severe course of SARS-CoV-2 infection. Materials and Methods: The following peripheral blood combination biomarkers were calculated: NLR (neutrophil/lymphocytes ratio), LMR (lymphocyte/monocyte ratio), PLR (platelet/lymphocyte ratio), dNLR (neutrophils/(white blood cells - neutrophils)), NLPR (neutrophil/(lymphocyte × platelet ratio)) in 374 patients who were admitted to the Temporary Hospital no 2 of Clinical Hospital in Bialystok (Poland) with COVID-19. The patients were divided into four groups depending on the severity of the course of COVID-19 using MEWS classification. Results: The NLR and dNLR were significantly increased with the severity of COVID-19, according to MEWS score. The AUC for the assessed parameters was higher in predicting death in patients with COVID-19: NLR (0.656, p=0.0018, cut-off=6.22), dNLR (0.615, p=0.02, cut-off=3.52) and LMR (0.609, p=0.03, cut-off=2.06). Multivariate COX regression analysis showed that NLR median above 5.56 (OR: 1.050, P=0.002), LMR median below 2.23 (OR: 1.021, P=0.011), and age >75 years old (OR: 1.072, P=0.000) had a significant association with high risk of death during COVID-19. Conclusion: Our results indicate that NLR, dNLR, and LMR calculated on admission to the hospital can quickly and easy identify patients with risk of a more severe course of COVID-19. Increase NLR and decrease LMR have a significant predictive value in COVID-19 patient's mortality and might be a potential biomarker for predicting death in COVID-19 patients.

The Diagnostic Value of Inflammatory Markers (CRP, IL6, CRP/IL6, CRP/L, LCR) for Assessing the Severity of COVID-19 Symptoms Based on the MEWS and Predicting the Risk of Mortality.

Introduction: Various diagnostic tools are used to assess the severity of COVID-19 symptoms and the risk of mortality, including laboratory tests and scoring indices such as the Modified Early Warning Score (MEWS). The diagnostic value of inflammatory markers for assessing patients with different severity of COVID-19 symptoms according to the MEWS was evaluated in this study. Materials and Methods: The concentrations of CRP (C-reactive protein) (immunoassay) and IL6 (interleukin 6) (electrochemiluminescence assay) were determined, and CRP/IL6, CRP/L, and LCR ratios were calculated in blood serum samples collected from 374 COVID-19 patients. Results: We demonstrated that CRP, IL6, CRP/IL6, CRP/L, LCR inflammatory markers increase significantly with disease progression assessed based on the MEWS in COVID-19 patients and may be used to differentiating patients with severe and non-severe COVID-19 and to assess the mortality. Conclusion: The diagnostic value of inflammatory markers for assessing the risk of mortality and differentiating between patients with mild and severe COVID-19 was confirmed.

miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala.

Severe psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour. Upon stress, miR-483-5p is upregulated in the synaptic compartment of amygdala neurons and directly represses three stress-associated genes: Pgap2, Gpx3 and Macf1. Upregulation of miR-483-5p leads to selective contraction of distal parts of the dendritic arbour and conversion of immature filopodia into mature, mushroom-like dendritic spines. Consistent with its role in reducing the stress response, upregulation of miR-483-5p in the basolateral amygdala produces a reduction in anxiety-like behaviour. Stress-induced neuromorphological and behavioural effects of miR-483-5p can be recapitulated by shRNA mediated suppression of Pgap2 and prevented by simultaneous overexpression of miR-483-5p-resistant Pgap2. Our results demonstrate that miR-483-5p is sufficient to confer a reduction in anxiety-like behaviour and point to miR-483-5p-mediated repression of Pgap2 as a critical cellular event offsetting the functional and behavioural consequences of psychological stress.

Clinical Significance and Diagnostic Utility of NLR, LMR, PLR and SII in the Course of COVID-19: A Literature Review.

Nowadays, society is increasingly struggling with infectious diseases that are characterized by severe course and even death. Recently, the whole world has faced the greatest epidemiological threat, which is COVID-19 caused by SARS CoV-2 virus. SARS CoV-2 infection is often accompanied by severe inflammation, which can lead to the development of different complications. Consequently, clinicians need easily interpreted and effective markers of inflammation that can predict the efficacy of the treatment and patient prognosis. Inflammation is associated with changes in many biochemical and hematological parameters, including leukocyte counts and their populations. In COVID-19, changes in leukocytes count populations such as neutrophils, lymphocytes or monocytes are observed. The numerous research confirm that indicators like neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII) may prove effective in assessment patient prognosis and choosing optimal therapy. Therefore, in this review, we would like to summarize the latest knowledge about the diagnostic utility of systemic inflammatory ratios - NLR, LMR, PLR and SII in patients with COVID-19. We focused on the papers evaluating the diagnostic utility of inflammatory ratios using ROC curve published in the recent 3 years. Identification of biomarkers associated with inflammation would help the selection of patients with severe course of COVID-19 and high risk of death.

Fashionable, but What is Their Real Clinical Usefulness? NLR, LMR, and PLR as a Promising Indicator in Colorectal Cancer Prognosis: A Systematic Review.

The link between inflammation and cancer is still an attractive subject of many studies because systemic inflammatory response has been proven to play a pivotal role in cancer progression and metastasis. The strongest relationship between chronic inflammation and cancer development is observed in colorectal cancer (CRC). The evaluation of ratios derived from the routinely performed inflammatory biomarkers shows limited performances and limited clinical utility when individually used as prognostic factors for patients with CRC. In this review, we would like to summarize the latest knowledge about the diagnostic utility of systemic inflammatory ratios: neutrophil/lymphocyte (NLR), lymphocyte/monocyte (LMR), and platelet/lymphocyte (PLR) in CRC. We focused on the papers that assessed the diagnostic utility of blood cell parameters on the basis of the area under the ROC curve published in the recent 6 years. Identification of biomarkers that are significantly associated with prognostic in cancer would help the selection of patients with a high risk of poor outcomes.

Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study.

Aim: The 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 methods: The 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. Results: The study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-ß, 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. Conclusions: MIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.

Canonical NF-κB signaling pathway and GRO-α/CXCR2 axis are activated in unruptured intracranial aneurysm patients.

Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.

Matrix Metalloproteinase 9 (MMP-9) and Interleukin-8 (IL-8) in Gingival Crevicular Fluid after Regenerative Therapy in Periodontal Intrabony Defects with and without Systemic Antibiotics-Randomized Clinical Trial.

The aim of our study was to assess changes in the levels of IL-8 and MMP-9 in gingival crevicular fluid (GCF) collected from the periodontal pocket before and after regenerative surgery with deproteinized bovine bone mineral (DBBM) and collagen membrane (GTR) either independently (DBBM/GTR) or with the postoperative administration of antibiotic (DBBM/GTR+AB). The study involved 41 patients, each with one intrabony defect. IL-8 and MMP-9 were determined before therapy and after 2 weeks, 4 weeks and 6 months following the surgical procedure by means of dedicated ELISA kits. No statistical differences were observed in the levels of IL-8 and MMP-9 after 2 weeks, 4 weeks and 6 months between the groups. The changes in the level of MMP-9 over time were not statistically significant in any group. The changes in the level of IL-8 were significant for the group given antibiotic but not in the nonantibiotic group in the follow-up period. IL-8 and MMP-9 were found to correlate positively but not after 4 weeks in the test group. Current assessment of IL-8 and MMP-9 obtained from GCF samples provides evidence that collagen matrix turnover occurs actively during the early healing phase in the periodontium after regenerative procedures. We observed positive correlations of MMP-9 and IL-8 throughout the study. However, we failed to reveal any differences regard parameters studied between the two groups.

IL-6 Quotient (The Ratio of Cerebrospinal Fluid IL-6 to Serum IL-6) as a Biomarker of an Unruptured Intracranial Aneurysm.

BACKGROUND: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth. METHODS: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers' instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6. RESULTS: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p<0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p<0.001). In both the study and control group, the blood-brain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227). CONCLUSION: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.

Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour.

INTRODUCTION: Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours. PATIENTS AND METHODS: Protein concentration in primary brain tumour (n = 49) and non-tumoural subjects (n = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-µm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein. RESULTS: The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients. CONCLUSIONS: Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients' survival.

Association of Tumour Microenvironment with Protein Glycooxidation, DNA Damage, and Nitrosative Stress in Colorectal Cancer.

PURPOSE: 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.

The Relationship between Inflammation Markers (CRP, IL-6, sCD40L) and Colorectal Cancer Stage, Grade, Size and Location.

The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/µL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed.

Dynamics of Matrix Metalloproteinase-1 and -8 Secretion in Gingival Crevicular Fluid after Gingival Recession Therapy via MCAT with Either Subepithelial Connective Tissue Graft or Collagen Matrix.

OBJECTIVES: The objective of this study was to determine and estimate the changing levels of matrix metalloproteinases 1 and 8 (MMP-1 and MMP-8) in GCF at consecutive stages of healing after root coverage procedure via modified coronally advanced tunnel (MCAT) combined with either sub-epithelial connective tissue graft (SCTG) or collagen matrix (CM) and also to relate those changes to clinical outcomes of both therapeutic approaches. MATERIALS AND METHODS: The study involved 20 patients with a total of 91 recessions. Those on one side of the mandible received MCAT plus CM while the contralateral ones MCAT plus SCTG. The evaluation of MMP-1 and MMP-8 concentrations in Gingival Crevicular Fluid (GCF) took place at baseline, then at 1, 2, and 4 weeks, and finally at 3 months after surgery. Elisa protocol was applied to determine the levels of MMP-1 and MMP-8 in GCF. RESULTS: Three-month observation revealed statistically significant changes in MMP-1, MMP-8 and Sulcus Fluid Flow Rate (SFFR) values after implementation of both techniques. A correlation was found between a difference in MMP-1 concentrations and gain in Keratinized Tissue (KT) after SCTG and CM. MMP-8 levels and a Gingival Thickness (GT) gain observed after CM was also correlated. CONCLUSIONS: A type of augmentative material does appear to determine the dynamics of MMP-1 secretion.

Sirtuins-The New Important Players in Women's Gynecological Health.

The participation of sirtuins in the regulation of oxidative stress and inflammation lies at the basis of their possible modes of action and is related to their expression in various cell structures; their location in the mitochondria and blood plasma has been indicated as of primary importance. Despite many existing studies, research on sirtuins continues to present an opportunity to discover new functions and dependencies, especially when it comes to women's gynecological health. Sirtuins have a significant role in both the formation and the course of many gynecological diseases. Their role is particularly important and well documented in the course of the development of cancer within the female reproductive organs; however, disturbances observed in the ovary and oocyte as well as in follicular fluid are also widely investigated. Additionally, sirtuins take part in some gynecological disturbances as regulative factors in pathways associated with insulin resistance, glucose and lipids metabolism disorders. In this review, we would like to summarize the existing knowledge about sirtuins in the manner outlined above.

Inflammatory cell-associated tumors. Not only macrophages (TAMs), fibroblasts (TAFs) and neutrophils (TANs) can infiltrate the tumor microenvironment. The unique role of tumor associated platelets (TAPs).

It is well known that various inflammatory cells infiltrate cancer cells. Next to TAMs (tumor-associated macrophages), TAFs (tumor-associated fibroblasts) and TANs (tumor-associated neutrophils) also platelets form the tumor microenvironment. Taking into account the role of platelets in the development of cancer, we have decided to introduce a new term: tumor associated platelets-TAPs. To the best of our knowledge, thus far this terminology has not been employed by anyone. Platelets are the first to appear at the site of the inflammatory process that accompanies cancer development. Within the first few hours from the start of the colonization of cancer cells platelet-tumor aggregates are responsible for neutrophils recruitment, and further release a number of factors associated with tumor growth, metastasis and neoangiogenesis. On the other hand, it also has been indicated that factors delivered from platelets can induce a cytotoxic effect on the proliferating neoplastic cells, and even enhance apoptosis. Undoubtedly, TAPs' role seems to be more complex when compared to tumor associated neutrophils and macrophages, which do not allow for their division into TAP P1 and TAP P2, as in the case of TANs and TAMs. In this review we discuss the role of TAPs as an important element of tumor invasiveness and as a potentially new therapeutic target to prevent cancer development. Nevertheless, better exploring the interactions between platelets and tumor cells could help in the formulation of new therapeutic goals that support or improve the effectiveness of cancer treatment.