20S constitutive proteasome, 20S immunoproteasome, and cathepsin S are high-sensitivity and independent markers of immunological activity in relapsing-remitting type of multiple sclerosis.

Research on the markers of autoimmune response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations as potential biomarkers of a relapsing-remitting type of MS (RRMS). Surface plasmon resonance imaging (SPRI) biosensors were used for the evaluation of protein concentrations. Plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations were significantly higher in RRMS patients compared to the control group. All three parameters were characterized by excellent usefulness in differentiating MS patients from healthy individuals (AUC equal to or close to 1.000). The plasma concentration of analyzed parameters was not correlated with severity of disability in the course of RRMS (EDSS value), the number of years from the first MS symptoms, the number of years from MS diagnosis, or the number of relapses within the 24-month observational period. Our study has shown that plasma concentrations of 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S have promising potential in differentiating RRMS patients from healthy individuals. All of the analyzed parameters were found to be independent of the time of MS relapse and the severity of neurological symptoms. Hence, their potential as highly sensitive and independent circulating markers of RRMS suggests a stronger association with immunological activity (inflammatory processes) than with the severity of the disease.

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

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

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.

Associations Between Mean Platelet Volume and Various Factors in Type 2 Diabetes Patients: A Single-Center Study from Poland.

BACKGROUND Thromboembolic episodes, which are largely mediated by blood platelets, are prevalent chronic complications of diabetes. The mean platelet volume (MPV) serves as a marker for in vivo platelet activation. This study aimed to assess the factors influencing MPV in 106 patients with type 2 diabetes, compared with 59 non-diabetic individuals at a single center in Poland. MATERIAL AND METHODS We performed linear regression analysis, with MPV as the dependent variable and factors such as age, sex, thrombopoiesis-influencing cytokines, blood pressure, body mass index, glycosylated hemoglobin percentage, platelet count, large platelet count, lipid profile parameters, creatinine concentration, estimated glomerular filtration rate, treatment modalities, and comorbidities as independent variables. MPV was measured using the ADVIA 2120 hematology analyzer, with a reference range of 7-12 fL. RESULTS The analysis revealed that in patients with type 2 diabetes, an increase in platelet count by 10×10³/µL resulted in a decrease in MPV by 0.05 (P<0.001), while an increase in large platelet count by 1×10³/µL led to an increase in MPV by 0.18 (P<0.001). Additionally, patients taking ß-blockers or insulin had lower MPVs by 0.77 (P=0.008) and 5.63 (P<0.001), respectively, compared with those not on these medications. CONCLUSIONS This study delineates the relationship between MPV, platelet parameters, and treatment modalities in type 2 diabetes, paving the way for further research to elucidate underlying mechanisms and potential clinical applications.

Cerebrospinal Fluid-Basic Concepts Review.

Cerebrospinal fluid plays a crucial role in protecting the central nervous system (CNS) by providing mechanical support, acting as a shock absorber, and transporting nutrients and waste products. It is produced in the ventricles of the brain and circulates through the brain and spinal cord in a continuous flow. In the current review, we presented basic concepts related to cerebrospinal fluid history, cerebrospinal fluid production, circulation, and its main components, the role of the blood-brain barrier and the blood-cerebrospinal fluid barrier in the maintenance of cerebrospinal fluid homeostasis, and the utility of Albumin Quotient (QAlb) evaluation in the diagnosis of CNS diseases. We also discussed the collection of cerebrospinal fluid (type, number of tubes, and volume), time of transport to the laboratory, and storage conditions. Finally, we briefly presented the role of cerebrospinal fluid examination in CNS disease diagnosis of various etiologies and highlighted that research on identifying cerebrospinal fluid biomarkers indicating disease presence or severity, evaluating treatment effectiveness, and enabling understanding of pathogenesis and disease mechanisms is of great importance. Thus, in our opinion, research on cerebrospinal fluid is still necessary for both the improvement of CNS disease management and the discovery of new treatment options.

UCHL1, besides leptin and fibronectin, also could be a sensitive marker of the relapsing-remitting type of multiple sclerosis.

Research on the markers of immunoregulatory response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of leptin, fibronectin, and UCHL1 concentrations as potential biomarkers of a relapsing-remitting type of MS (RRMS). Surface Plasmon Resonance Imaging (SPRI) biosensors were used for the evaluation of proteins concentrations in 100 RRMS patients and 46 healthy volunteers. Plasma leptin, fibronectin, and UCHL1 concentrations were significantly higher in RRMS patients compared to the control group (p < 0.001, respectively). UCHL1 concentration evaluation revealed the highest diagnostic sensitivity (100%) and negative predictive value (100%) in differentiating MS patients from healthy individuals. There was no significant difference in the UCHL1 concentrations depending on the patient's sex, the presence of relapse within the last 24 months, and the EDSS value (p > 0.05, respectively). In RRMS patients UCHL1 concentration positively correlated with fibronectin levels (r = 0.3928; p < 0.001). In the current cohort of patients plasma UCHL1 concentration was independent of the time of MS relapse and the severity of neurological symptoms. Thus current study may indicate that plasma UCHL1, besides leptin and fibronectin, also could be a promising high-sensitive potential biomarker of relapsing-remitting type of MS. However, these results should be validated with a larger group of patients, taking into account neuroimaging and cerebrospinal fluid analysis data, and by comparing them to patients with other neurological diseases as a control group.

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.

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients.

Introduction: Identifying all the relevant "players" in the formation and development of brain aneurysms may help understand the mechanisms responsible for the formation of an aneurysm, as well as in the search for non-invasive targets for aneurysm pharmacotherapy. Aim: The evaluation of the concentration of pro-inflammatory and anti-inflammatory cytokines in cerebrospinal fluid (CSF) and serum of patients with unruptured intracranial aneurysms (UIA) in comparison to individuals without vascular lesions in the brain. Methods: The concentration of 27 proteins in the CSF and serum of UIA patients (N = 40) and individuals without vascular lesions in the brain (N = 15) was evaluated using a multiplex ELISA kit (Bio-Plex Pro Human Cytokine 27-Plex Panel). Results: In the CSF 13 out of 27 proteins evaluated presented a concentration 1.36-fold or greater in UIA patients in comparison to the control group. Significantly higher were IL-1ß, IL-1ra, IL-2, IL-4, IL-5, IL-7, IL-8, IL-12, IL-13, TNF-α, INF-γ, MCP-1, and VEGF. In the serum none of the proteins evaluated significantly differ between UIA patients and the control group. The correlation coefficient analysis showed that CSF IL-1ß, IL-8, and TNF-α positively, while IL-13 negatively correlated with the size of aneurysms. CSF IL-6 and MCP-1 concentrations positively correlated with the number of aneurysms. Conclusion: In patients with UIA, pro-inflammatory and anti-inflammatory mechanisms are activated simultaneously, because the concentration of promoting and suppressing inflammatory response proteins was significantly higher in CSF of UIA patients compared to the control group. The preventive therapy of brain aneurysm development should be focused on IL-1ß, IL-6, IL-8, MCP-1, and TNF-α, the concentration of which in CSF positively correlated with the size and number of aneurysms.

The Concentration of Selected Inflammatory Cytokines (IL-6, IL-8, CXCL5, IL-33) and Damage-Associated Molecular Patterns (HMGB-1, HSP-70) Released in an Early Response to Distal Forearm Fracture and the Performed Closed Reduction With Kirschner Wire Fixation in Children.

The evaluation of trauma after surgery through objective analysis of biochemical markers can help in selecting the most appropriate therapy. Thus the aim of the study was the evaluation of the concentration of selected inflammatory cytokines (IL-6, IL-8, CXCL5, IL-33), C-reactive protein (CRP), and damaged-associated molecular patterns (DAMPs): HMGB-1, HSP-70 in the plasma of children in response to bone fracture and 12-14 hours after subsequent surgery performed by closed reduction with percutaneous Kirschner wire fixation (CRKF). The study will answer the question if the CRFK procedure leads to excessive production of inflammatory and damage markers. Blood samples from 29 children with distal forearm fractures were collected 30 min. before CRKF procedure and 12-14 hours after performance of the procedure. The control group was composed of 17 healthy children. IL-6 and CRP concentrations were analyzed using routinely performed in vitro diagnostics tests; the remaining proteins were analyzed with the use of the ELISA method. Increased values of IL-6, CRP, and HSP-70 represented an early inflammatory response to distal forearm fractures classified as SH-II type according to the Salter-Harris classification system. However, the median CRP concentration was within the reference values not indicative of inflammation. The CRKF procedure may be a good solution for the treatment of bone fractures, as damaged associated molecular patterns - HMGB-1 and HSP-70 - did not significantly differ 12-14 hours after the approach was applied as compared to the control group. Moreover, the increase in IL-6 concentration after the CRKF procedure was 1.5-fold to the level before CRKF, while the increase of this marker in response to the distal forearm fracture was 4.3-fold compared to the control group. Based on this data, it appears reasonable to suggest that the CRKF approach caused less damage and inflammatory response in comparison to the response to the fracture itself.

Impact of the SARS-CoV-2 pandemic on the course and treatment of appendicitis in the pediatric population.

SARS-CoV-2 is a highly contagious virus causing mainly respiratory track disease called COVID-19, which dissemination in the whole world in the 2020 has resulted in World Health Organisation (WHO) announcing the pandemic. As a consequence Polish Government made a decision to go into a lockdown in order to secure the population against SARS-CoV-2 outbreak what had its major influence on the Polish Health Care System. All of the social and medical factors caused by the pandemic might influence children's health care, including urgent cases. The aim of this survey was the analysis of medical charts with focus on the course and results of surgical treatment of children who underwent appendectomy before and during the COVID-19 pandemic. Material and methods: We performed analysis of charts of 365 subjects hospitalized in the Pediatric Surgery Department from 1st January 2019 to 31st December 2020 because of acute appendicitis. Patients were divided into two groups-those treated in 2019-before pandemic outbreak, and those treated in 2020 in the course of pandemic. Results: the most common type of appendicitis was phlegmonous (61% of cases in 2019 and 51% of cases in 2020). Followed by diffuse purulent peritonitis (18% of cases in 2019 vs 31% of cases in 2020), gangrenous (19% of cases in 2019 vs 15% of cases in 2020) and simple superficial appendicitis (1% of cases in 2019 vs 3% of cases in 2020). There was statistically significant difference in the length of hospitalization: in 2019 the mean length of hospi-talization was 4.761 vs 5.634 in 2020. Laparoscopic appendectomy was performed more frequently before the COVID period (63% of cases treated in 2019 vs 61% of cases treated in 2020). In the pandemic year 2020, there was double increase in the number of conversion from the laparoscopic approach to the classic open surgery. In the year 2019 drainage of abdominal cavity was necessary in 22% of patients treated with appendectomy, in 2020 the amount of cases threated with appendectomy and drainage increased to 32%. Conclusions: fear of being infected, the limited availability of appointments at General Practitioners and the new organisation of the medical health care system during pandemic, delay proper diagnosis of appendicitis. Forementioned delay leads to higher number of complicated cases treated with open appendectomy and drainage of abdominal cavity, higher number of conversions from the laparoscopic to classic open technique, and longer hospitalization of children treated with appendectomy in the year of pandemic.

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.

Effects of combined Pulsed Dye Laser and Fractional CO2 Laser treatment of burn scars and correlation with plasma levels of collagen type I, MMP-2 and TIMP-1.

Hypertrophic burn scars remain a significant burden for patients and a challenge for clinicians. THE AIM: Assessement of the efficacy of combined Pulsed Dye Laser and Ablative Fractional CO2 Laser therapy on hyperthophic scars and correlation with plasma levels of MMP-2, TIMP-1 and alpha-1 type I collagen. PATIENTS AND METHODS: Twenty five pediatric subjects were enrolled into the study. Control group consisted of age-matched subjects admitted for surgical repair of inguinal hernia. For the assessment of the results of laser treatment we used the Vancouver scar scale (VSS), and Patient-Observer Scar Assessment Scale (POSAS). We also correlated clinical results with plasma levels of MMP-2, TIMP-1 and alpha-1 type I collagen. RESULTS: All subjects reported the laser treatment resulted in improvement and were somewhat satisfied or very satisfied with their experience. No adverse events were reported. The levels of MMP-2, TIMP-1 and alpha-1 type I collagen in our patients with scars before laser threatment were higher in comparison to controls. We also found statistically significant decrease in the levels of MMP-2, TIMP-1 and alpha-1 type I collagen after laser treatment of burn scars CONCLUSIONS: Our study clearly shows that combined CO2-AFL treatment for burn scars improve texture, colour, function and alleviate pruritus. We believe that decrease in the levels of MMP-2, TIMP-1 and alpha-1 type I collagen after laser treatment of burn scars, reflects reduced dynamic of scar.

BDNF and IL-8, But Not UCHL-1 and IL-11, Are Markers of Brain Injury in Children Caused by Mild Head Trauma.

The aim of the study was to check whether the plasma levels of brain-derived neurotrophic factor (BDNF), interleukin-8 (IL-8), interleukin-11 (IL-11) and ubiquitin C-terminal hydrolase L1 (UCHL-1) change in children with mild head trauma (N = 29) compared to controls (N = 13). Protein concentration in children with mild head trauma (12 children with mild concussion without loss of consciousness and 17 children with severe concussion and loss of consciousness) and the control group were measured by means of the Enzyme-Linked Immunosorbent Assay (ELISA) method. IL-8 and BDNF concentration was statistically higher in the group of children with mild head trauma (9.89 pg/mL and 2798.00 pg/mL, respectively) compared to the control group (7.52 pg/mL and 1163.20 pg/mL, respectively). BDNF concentration was significantly higher in children with severe concussion and loss of consciousness (3826.00 pg/mL) than in the control group. None of the tested proteins differed significantly between children with mild concussion without loss of consciousness and children with severe concussion and loss of consciousness. BDNF and IL-8 may be sensitive markers of brain response to mild head trauma in children. The lack of statistical differences for BDNF and IL-8 between children with mild or severe concussion could indicate that their elevated levels may not result from significant structural brain damage but rather reflect a functional disturbance.

Elevated plasma 20S proteasome chymotrypsin-like activity is correlated with IL-8 levels and associated with an increased risk of death in glial brain tumor patients.

INTRODUCTION: In cancer treatment an attempt has been made to pharmacologically regulate the proteasome functions, thus the aim was to test whether 20S proteasome chymotrypsin-like (ChT-L) activity has a role in glial brain tumors. Furthermore, we analyzed the correlation between proteasome activity and IL-8, CCL2, NF-κB1 and NF-κB2 concentrations, which impact on brain tumors has already been indicated. METHODS: Plasma 20S proteasome ChT-L activity was assayed using the fluorogenic peptide substrate Suc-Leu-Leu-Val-Tyr-AMC in the presence of SDS. IL-8, CCL2, NF-κB1 and NF-κB2 concentration was analyzed with the use of ELISA method. Immunohistochemistry for IDH1-R132H was done on 5-microns-thick formalin-fixed, paraffin-embedded tumor sections with the use of antibody specific for the mutant IDH1-R132H protein. Labelled streptavidin biotin kit was used as a detection system. RESULTS: Brain tumor patients had statistically higher 20S proteasome ChT-L activity (0.649 U/mg) compared to non-tumoral individuals (0.430 U/mg). IDH1 wild-type patients had statistically higher 20S proteasome ChT-L activity (1.025 U/mg) compared to IDH1 mutants (0.549 U/mg). 20S proteasome ChT-L activity in brain tumor patients who died as the consequence of a tumor (0.649) in the following 2 years was statistically higher compared to brain tumor patients who lived (0.430 U/mg). In brain tumor patients the 20S proteasome ChT-L activity positively correlated with IL-8 concentration. CONCLUSIONS: Elevated 20S proteasome ChT-L activity was related to the increased risk of death in glial brain tumor patients. A positive correlation between 20S proteasome ChT-L activity and IL-8 concentration may indicate the molecular mechanisms regulating glial tumor biology. Thus research on proteasomes may be important and should be carried out to verify if this protein complexes may represent a potential therapeutic target to limit brain tumor invasion.

Diagnostic utility of protein to creatinine ratio (P/C ratio) in spot urine sample within routine clinical practice.

The spot (random) urine protein to creatinine ratio (P/C ratio) is an alternative, fast and simple method of detecting and estimating the quantitative assessment of proteinuria. The aim of the work was to review the literature concerning the usefulness of spot urine P/C ratio evaluation in the diagnosis of proteinuria in the course of kidney disease, hypertension, gestational hypertension, preeclampsia, immunological diseases, diabetes mellitus, and multiple myeloma, and in the diagnosis of proteinuria in children. We searched the PubMed and Google Scholar databases using the following keywords: proteinuria, spot urine protein to creatinine ratio, spot urine P/C ratio, protein creatinine index, PCR (protein to creatinine ratio), P/C ratio and methods, Jaffe versus enzymatic creatinine methods, urine protein methods, spot urine protein to creatinine ratio versus ACR (albumin to creatinine ratio), proteinuria versus albuminuria, limitations of the P/C ratio. More weight was given to the articles published in the last 10-20 years. A spot urine P/C ratio >20 mg/mmol (0.2 mg/mg) is the most commonly reported cutoff value for detecting proteinuria, while a P/C ratio value >350 mg/mmol (3.5 mg/mg) confirms nephrotic proteinuria. The International Society for the Study of Hypertension in Pregnancy recommends a P/C ratio of 30 mg/mmol (0.3 mg/mg) for the classification of proteinuria in pregnant women at risk of preeclampsia. A high degree of correlation was observed between P/C ratio values and the protein concentration in 24-h urine collections. The spot urine P/C ratio is a quick and reliable test that can eliminate the need for a daily 24-h urine collection. However, in doubtful situations, it is still recommended to assess proteinuria in a 24-h urine collection. The literature review indicates the usefulness of the spot P/C ratio in various disease states; therefore, this test should be available in every laboratory. However, the challenge for the primary care physician is to know the limitations of the methods used to determine the protein and creatinine concentrations that are used to calculate the P/C ratio. Moreover, the P/C ratio cutoff used should be determined in individual laboratories because it depends on the patient population and the laboratory methodologies.

Mean Platelet Volume (MPV): New Perspectives for an Old Marker in the Course and Prognosis of Inflammatory Conditions.

Platelet size has been demonstrated to reflect platelet activity and seems to be a useful predictive and prognostic biomarker of cardiovascular events. It is associated with a variety of prothrombotic and proinflammatory diseases. The aim is a review of literature reports concerning changes in the mean platelet volume (MPV) and its possible role as a biomarker in inflammatory processes and neoplastic diseases. PubMed database was searched for sources using the following keywords: platelet activation, platelet count, mean platelet volume and: inflammation, cancer/tumor, cardiovascular diseases, myocardial infarction, diabetes, lupus disease, rheumatoid arthritis, tuberculosis, ulcerative colitis, renal disease, pulmonary disease, influencing factors, age, gender, genetic factors, oral contraceptives, smoking, lifestyle, methods, standardization, and hematological analyzer. Preference was given to the sources which were published within the past 20 years. Increased MPV was observed in cardiovascular diseases, cerebral stroke, respiratory diseases, chronic renal failure, intestine diseases, rheumatoid diseases, diabetes, and various cancers. Decreased MPV was noted in tuberculosis during disease exacerbation, ulcerative colitis, SLE in adult, and different neoplastic diseases. The study of MPV can provide important information on the course and prognosis in many inflammatory conditions. Therefore, from the clinical point of view, it would be interesting to establish an MPV cut-off value indicating the intensity of inflammatory process, presence of the disease, increased risk of disease development, increased risk of thrombotic complications, increased risk of death, and patient's response on applied treatment. Nevertheless, this aspect of MPV evaluation allowing its use in clinical practice is limited and requires further studies.

Association of PTPN22 polymorphism and its correlation with Graves' disease susceptibility in Polish adult population-A preliminary study.

BACKGROUND: Susceptibility to Graves' disease (GD) is determined by various genetic factors; the gene encoding protein tyrosine phosphatase (PTPN22) may be one of those associated with higher risk of GD. The aim was to estimate the association of the PTPN22 gene polymorphism rs2476601:c.C>T (c.1858C>T) with the predisposition to GD within the adult north-eastern Polish population. METHODS: PTPN22 gene polymorphism was analyzed in individuals with clinical GD history (n = 166) and healthy subjects (n = 154). The presence of different variants of the investigated gene polymorphism was estimated using the DNA Sanger sequencing method. RESULTS: Patients with GD had a more frequent occurrence of the T gene allele of PTPN22 gene compared to the control group, however, it was not significant (p = 0.257). Analysis of genotype distribution showed significantly more frequent occurrence of TT homozygote in GD patients compared to control individuals (p = 0.016, OR = 9.28). Patients with ophthalmopathy had a less frequent occurrence of the T gene allele of PTPN22 gene compared to patients without ophthalmopathy, however, it was not significant (p = 0.12). Occurrence of the T gene allele of PTPN22 gene in GD manifestation in those under 40-year old was more frequent compared to individuals over 40, but the obtained difference was also not significant (p = 0.75). CONCLUSIONS: Our preliminary study suggest that PTPN22:c.1858C>T gene polymorphism may be associated with a predisposition to GD within the adult north-eastern Polish population. The studied polymorphism of the PTPN22 gene did not significantly affect the risk of ophthalmopathy developing and disease manifestation before the age of 40.