Bladder cancer (BCa) is the most frequently diagnosed malignancy of the urinary system and is characterized by a multifactorial etiology. Multiple growth factors have been implicated in BCa progression. This cross-sectional study investigated whether the pro-angiogenic factors angiopoietin-like 4 (ANGPTL4), insulin-like growth factor 1 (IGF-1), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) could differentiate BCa patients according to the degree of systemic inflammation. Based on histopathological examination, 101 participants were enrolled and divided into a cancer group (CG; n = 69), and a non-cancer group (NCG; n = 32), comprising patients who were not diagnosed with BCa following histopathological evaluation. Healthy control was also recruited from Blood Donor Repository (n = 34). The control group was younger (median min-max years old; CG: 71 (48-92); NCG: 70 (26-86); control: 43 (28-61); p < 0.0001) and had a lower body mass index (BMI) compared to the CG and NCG groups (median min-max kg/m2; CG: 27 (21-43); NCG: 27 (19-37); control: 21 (20-31); p < 0.0001). The CG was stratified by median C-reactive protein (CRP) level (4.53 μg/mL) and further analyzed. Regardless of CRP level, patients in both the CG and NCG groups had higher concentrations of all assessed proangiogenic and proinflammatory markers than healthy controls. Individuals with BCa, regardless of CRP level, were more likely to be smokers compared with NCG (p < 0.001), which was confirmed in a multivariate analysis pointing to smoking as the only variable that significantly differentiated the CG from the NCG (OR = 3.78, 95% CI: 1.36-10.54, p = 0.0109). No significant differences in tumor grade or TNM classification were observed between the low-CRP and high-CRP subgroups. Analysis of inflammatory parameters revealed significant differences in CRP concentrations alone. The high-CRP CG subgroup exhibited significantly higher CRP levels compared with both the low-CRP CG subgroup and the NCG (p < 0.0001). Analysis of proangiogenic markers revealed differences only in VEGF. No significant differences were observed for ANGPTL4, IGF-1, and FGF21, as well as in the counts of leucocytes and platelets.VEGF concentrations differed significantly between subgroups and were highest in the high-CRP CG subgroup compared with the low-CRP CG subgroup and the NCG (median pg/mL: 186.7 vs. 120.5 vs. 120.6, respectively; p = 0.0330). Receiver operating characteristic (ROC) curve analysis of VEGF concentrations showed modest discriminative ability between CG and NCG, with an area under the curve (AUC) of 0.624 (95% CI: 0.529-0.719; p = 0.013). In the CG, multivariable linear regression showed that CRP was independently associated with higher VEGF levels after adjustment for smoking, tumor stage, age, sex, and BMI (β coefficient [95% CI) 0.302 [0.078;0.526]; p = 0.009), corresponding to an approximately 23.3% increase in VEGF for each twofold increase in CRP. Conclusion: These findings indicate that systemic inflammation, reflected by CRP levels, is independently associated with higher VEGF concentrations in BCa patients, supporting a potential link between inflammation and tumor-related angiogenesis.

Peritoneal fibrosis is a consequence of peritoneal dialysis, initiated by an inflammatory response in the peritoneum, whereas peritoneal adhesions represent intra-abdominal post-inflammatory complications. Given that the nuclear factor kappa B (NF-κB) signaling pathway plays a central role in inflammation, this systematic review aims to compile research findings on the role of NF-κB in peritoneal fibrosis and adhesions. Following the PRISMA 2020 guidelines, literature searches were conducted in PubMed, Scopus, and Web of Knowledge. Inclusion criteria covered research articles investigating NF-κB in peritoneal fibrosis and adhesions. Selected studies were categorized based on NF-κB-mediated regulation and NF-κB-targeted therapies. To date, the role of NF-κB in peritoneal fibrosis and adhesions has been described in 39 publications: 29 on fibrosis, 9 on adhesions, and 1 addressing both conditions. NF-κB activation was reported in human and animal studies, both in vitro and in vivo, in response to stimuli such as high glucose, inflammatory cytokines, growth factor, bacteria, and irritants. This activation led to upregulation of specific inflammatory, mesothelial-to-mesenchymal transition, fibrosis, and angiogenesis markers. All 21 therapeutic studies demonstrated inhibition of NF-κB activity and downregulation of related molecular markers-15 in fibrosis and 6 in adhesions. Controlling NF-κB activity in the peritoneal mesothelium may be beneficial in managing peritoneal dialysis and preventing peritoneal post-inflammatory complications.

BackgroundPeritoneal dialysis induces an intraperitoneal inflammatory reaction, which causes damage to the peritoneum. Inflammation also accelerates cellular senescence. We studied in vitro effect of the dialysates from peritoneal dialysis patients on the senescence of the peritoneal mesothelial cells (MCs). The effect of N-acetylcysteine (NAC) on that process was studied.MethodsReplicative senescence was induced in MC cells exposed to culture medium, medium mixed with the dialysate ± NAC 0.025 mmol/L. After 10 passages, markers of the cellular senescence and secretory activity of the cells were measured. Additionally, the effect of NAC on the senescent cells was studied.ResultsExposure of MC to the dialysate accelerated, more than in medium alone, their senescence as reflected by elongation of the population doubling time, increased expression of p21, p53 genes and β-galactosidase activity. Secretion of IL6 and transforming growth factor β (TGFβ) was increased, and fibrinolytic activity, as reflected by the tissue plasminogen activator/plasminogen activator inhibitor-1 ratio, was reduced. NAC slowed down the process of senescence in MC treated with the dialysate. NAC suppressed the proinflammatory properties of the senescent MC.ConclusionThe proinflammatory properties of the peritoneal dialysate accelerate the senescence of MC. Decreased fibrinolytic activity of MC, increased secretion of IL6 and TGFβ may accelerate fibrosis of the peritoneum. Supplementation of NAC in patients treated with peritoneal dialysis may help preserve the peritoneum as the dialysis membrane.

The misalignment of sleep and eating patterns with biological cycles is a significant issue that could have detrimental effects on health and is prevalent among cancer patients. Sleep duration, chronotype, and nutrition may be linked to the presence of urothelial tract cancer. Bladder cancer is the most frequently diagnosed cancer in the urinary system. The study estimated bladder cancer patients’ nutrition behavior, sleep preferences, and chronotype. 101 patients were enrolled. Based on histopathological examination, they were divided into the cancer group (n = 69) and the non-cancer group (n = 32). Lifestyle was assessed through three questionnaires about sleep, chronotype patterns, and chrononutrition behaviors: social jet lag, eating jet lag, eating window, evening and morning latency. The analysis was also completed by assessing salivary alpha-amylase and immunoglobulin A (IgA). In cancer and non-cancer patients, we did not find differences between the chronotypes (p = 0.0634) or other measured factors. Most of the studied population did not present social or eating jet lag and morning or evening latency. In addition, the total sleep duration in these groups was similar 8.5 (5.0–13.0) vs 9.0 (5.0–11.5) hours per day (p > 0.99). The eating window did not differ between the groups (p = 0.061). Furthermore, the assessment of salivary alpha-amylase 193.9 U/ml (10.2–1173.0) and IgA 129.0 μg/ml (5.1–801.1) (p = 0.43; p = 0.18, respectively) showed no differences. In this preliminary study, we did not observe a domination of particular types of chronotypes in the cancer and non-cancer groups. Moreover, there were no significant changes in lifestyle and chrononutrition behavior, except weak difference between groups in eating window. However, it provides a robust foundation for further research and clinical applications.

Background. Intravenous iron therapy is used in treatment of anemia in uremic pa-tients. In patients treated with peritoneal dialysis iv. infused iron diffuses into the peritoneal cavity and may cause injury to the mesothelial cell. Methods. We studied effect of Iron Isomaltoside (IIS) in presence of NF-κβ inhibitor dehydroxymethyepoxyquinmicin (DHMEQ) on function of the peritoneal mesothelial cells. Experiments were performed on human peritoneal mesothelial cells in in vitro culture ex-posed to IIS 15 ug/dL ± DHMEQ 1 ug/mL. Intracellular oxidative stress, secretory activity and collagen synthesis in the cells were studied. Results. IIS induced oxidative stress in the mesothelial cells and that effect was weaker in presence of DHMEQ (-52%,p<0.001). In cells exposed to IIS increased expression of genes for IL6 (+74%,p<0.001), PAI-1 (+43%, p<0.01) and TGFβ (+53%,p<0.001) was observed and reduced for tPA (-36%,p<0.01). In presence of IIS increased secretion of IL6 (+56%, p<0.001), TGFβ (+49%,p<0.001) and PAI-1 (+51%, p<0.001) was observed whereas secretion of tPA was reduced (-25%, p0.001). DHMEQ reduced changes in genes and secre-tory activity caused by IIS. In presence of IIS synthesis of collagen in mesothelial cells was increased (+45%,p<0.001) and that effect was weaker (-25% vs. IIS, p<0001) when simulta-neously DHMEQ was used. Discussion. IIS induces proinflammatory changes in mesothelial cells, deteriorates their fibrinolytic activity and stimulates synthesis of collagen. All these effects are reduced when simultaneously NF-κβ inhibitor – DHMEQ is used.

BACKGROUND:AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation. AIM:We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory - esRAGE and cleaved - cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition. METHODS:Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR. RESULTS:The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR. CONCLUSION:Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

People differ in their preferred time for intellectual activities. Morningness-eveningness preferences describe the preferred time for performing daily activities and are determined by chronotype. Chronotype reflects circadian preference in humans and is divided into morning, intermediate, and evening types. Learning motivation is a key predictor of student success and may influence learning and study, academic performance, intention to continue medical research, and well-being. Helping students develop learning motivation may improve their educational achievement and health. There are opposing studies regarding chronotype and academic achievement. We hypothesized that chronotype affects the learning motivation of medical school students. We used the reduced Morningness-Eveningness Questionnaire (rMEQ), and the Motivated Strategies for Learning Questionnaire (MSLQ) for Russian, Polish, Japanese, and Australian students in the first and second years of medical university. A total of 540 medical students answered the questionnaires. The MSLQ contains six subscales: intrinsic goal orientation, extrinsic goal orientation, self-efficacy for learning and performance, control of learning beliefs, task value, and test anxiety. The rMEQ was used to classify the students into three types, which were morning (26.7

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.

Objective: Inflammation fl ammation and endothelial dysfunction are important venous changes in patients with chronic venous disease (CVD). The use of the venoactive drugs remains an important treatment modality for patients with CVD, reducing the severity of the CVD-related symptoms and swelling but also reducing inflammation fl ammation and protecting endothelial cells. In this research, the effects of the serum obtained from patients with CVD before and after sulodexide treatment were evaluated for in vivo and in vitro inflammatory fl ammatory markers and endothelial cell function. Methods: Inflammatory fl ammatory markers (IL-6, matrix metalloproteinase-9 [MMP-9], vascular cell adhesion molecule-1 [VCAM-1], and von Willebrand factor [vWF]) from the incompetent great saphenous veins (GSVs) and from the systemic venous circulation were studied in 10 patients with CVD (C2s) before and after 2 months of sulodexide (2 x 500 lipasemic units/d) therapy. Serum obtained from the vein blood before and after sulodexide treatment was evaluated for in vitro cultured human umbilical vein endothelial cell function. Results: The serum collected from lower leg incompetent GSVs had significantly fi cantly elevated levels of VCAM-1 (+29%, + 29%, P < . 001) compared with the serum from the systemic circulation. Endothelial cells exposed to the serum from the incompetent lower leg veins of the untreated CVD patients demonstrated higher stimulated synthesis of MMP-9 (+17%, + 17%, P < . 01), as well as increased markers of senescence (prolongation of population doubling time, b-galactosidase activity, and expression of p21 and p53 genes). CVD serum-induced senescent endothelial cells had a higher expression of genes regulating IL-6, MMP-9, VCAM-1, and vWF synthesis. The overall proinflammatory fl ammatory effect on endothelial cells by the serum collected from the incompetent GSVs was stronger as compared with the serum from the systemic circulation. Serum collected from the veins after sulodexide treatment caused lower levels of endothelial cell inflammatory fl ammatory markers as well as respective gene expression than serum obtained at the beginning of the study (before sulodexide treatment). Sulodexide application also reduced the inflammatory fl ammatory secretory activity of the senescent endothelial cells. Sulodexide treatment resulted in the decrease of the majority of the studied inflammatory fl ammatory parameters in both lower limb incompetent vein and systemic blood. Conclusions: In patients with CVD, there are significant fi cant differences between circulating inflammatory fl ammatory markers analyzed from the lower leg incompetent GSV segments compared with the systemic circulation, indicating a higher inflam- fl am- matory condition in CVD. Treatment with sulodexide reduces the proinflammatory fl ammatory and endothelial cell activation properties of the serum from patients with CVD. (J Vasc Surg Venous Lymphat Disord 2024;12:101941.) Clinical Relevance: The study documented the significant fi cant proinflammatory fl ammatory human vascular endothelial cell activation when exposed to the serum collected from the varicose veins as compared with the serum from the systemic circulation in patients with chronic venous disease (CVD). The inflammatory fl ammatory marker expression, endothelial dysfunction, and endothelial cell senescence transformation can be successfully controlled and downregulated by patients' exposure to the glycosaminoglycan (sulodexide) treatment. Further studies are needed to confirm fi rm if glycosaminoglycan application can prevent further CVD clinical progression due to potential CVD-related pathological processes' modulation and their downregulation.

BACKGROUND:Treatment of anemia in peritoneal dialysis patients often requires intravenous iron supplementation. Iron diffuses into the peritoneal cavity and is injurious to the peritoneum. We studied how intermittent exposure to iron changes the properties of the senescent peritoneal mesothelial cells (MC). METHODS:Replicative senescence was induced in MC in control medium (Con) or in control medium with intermittent exposure to iron isomaltoside 15 µg/dL (Con-IIS). After 10 passages properties of MC from both groups were compared to MC not exposed to replicative senescence. RESULTS:In senescent MC population doubling time was elongated, intracellular generation of free radicals and staining for β-galactosidase was stronger than in MC not exposed to replicative senescence. All these effects were stronger in MC intermittently exposed to IIS. In these cells intracellular iron content was also higher. Also expression of genes p21 and p53 was stronger in MC intermittently treated with IIS. In senescent cells higher release and expression of IL6 and TGFβ1 was observed and that effect was stronger in MC treated with iron. Senescent MC had reduced fibrinolytic activity, what may predispose to the peritoneal fibrosis. Synthesis of collagen was higher in senescent cells, more in MC treated with iron. CONCLUSION:MC aging results in change of their genotype and phenotype which lead to their profibrotic effect. Exposure to iron enhances these changes.

Severe acute respiratory syndrome coronavirus-2 causes hyperinflammation and activation of coagulation cascade and, as a result, aggravates endothelial cell dysfunction. N-acetylcysteine and Sulodexide have been found to mitigate endothelial damage. The influence on coronary artery endothelial cells of serum collected after 4 ± 1 months from coronavirus infection was studied. The concentrations of serum samples of interleukin 6, von Willebrand Factor, tissue Plasminogen Activator, and Plasminogen Activator Inhibitor-1 were studied. The cultures with serum of patients after coronavirus infection were incubated with N-acetylcysteine and Sulodexide to estimate their potential protective role. The blood inflammatory parameters were increased in the group of cultures incubated with serum from patients after coronavirus infection. Supplementation of the serum from patients after coronavirus infection with N-acetylcysteine or Sulodexide reduced the synthesis of interleukin 6 and von Willebrand Factor. No changes in the synthesis of tissue Plasminogen Activator were observed. N-acetylcysteine reduced the synthesis of Plasminogen Activator Inhibitor-1. N-acetylcysteine and Sulodexide increased the tPA/PAI-1 ratio. N-acetylcysteine may have a role in reducing the myocardial injury occurring in the post-COVID-19 syndrome. Sulodexide can also play a protective role in post-COVID-19 patients.

Diabetes mellitus may cause severe damage to retinal blood vessels. The central aim of this study was to test the hypothesis that sulodexide, a mixture of glycosaminoglycans, has a protective effect against hyperglycemia-induced endothelial dysfunction in the retina. Functional studies were performed in isolated porcine retinal arterioles. Vessels were cannulated and incubated with highly concentrated glucose solution (HG, 25 mM D-glucose) +/− sulodexide (50/5/0.5 μg/mL) or normally concentrated glucose solution (NG, 5.5 mM D-glucose) +/− sulodexide for two hours. Endothelium-dependent and endothelium-independent vasodilatation were measured by videomicroscopy. Reactive oxygen species (ROS) were quantified by dihydroethidium (DHE) fluorescence. Using high-pressure liquid chromatography (HPLC), the intrinsic antioxidant properties of sulodexide were investigated. Quantitative PCR was used to determine mRNA expression of regulatory, inflammatory, and redox genes in retinal arterioles, some of which were subsequently quantified at the protein level by immunofluorescence microscopy. Incubation of retinal arterioles with HG caused significant impairment of endothelium-dependent vasodilation, whereas endothelium-independent responses were not affected. In the HG group, ROS formation was markedly increased in the vascular wall. Strikingly, sulodexide had a protective effect against hyperglycemia-induced ROS formation in the vascular wall and had a concentration-dependent protective effect against endothelial dysfunction. Although sulodexide itself had only negligible antioxidant properties, it prevented hyperglycemia-induced overexpression of the pro-oxidant redox enzymes, NOX4 and NOX5. The data of the present study provide evidence that sulodexide has a protective effect against hyperglycemia-induced oxidative stress and endothelial dysfunction in porcine retinal arterioles, possibly by modulation of redox enzyme expression.

Introduction Physiological and biochemical processes in the human body occur in a specific order and show rhythmic variability. Time dependence characterizes the secretion of cortisol and dehydroepiandrosterone (DHEA). One-day fasting implies alternating fasting days and eating days. The study aimed to determine how 24-h fasting affects the daily rhythm of cortisol and DHEA levels in obese people while taking into account gender and chronotype. Methods Forty-nine obese patients (BMI 32.2–67.1 kg/m 2 ; 25 women and 24 men) underwent a 3-week hospital-controlled calorie restriction diet to reduce body weight. During hospitalization, patients fasted for 1 day, during which only water could be consumed. Samples of whole mixed unstimulated saliva were collected at 2–3-h intervals over a 64-h period and analyzed for cortisol and DHEA by immunoassays. The individual chronotypes were assessed by the morning and evening questionnaire, according to Horne and Östberg. Three components of daily rhythm were evaluated: amplitude, acrophase, and the so-called MESOR. Results Cortisol rhythm showed differences in amplitude ( p = 0.0127) and acrophase ( p = 0.0005). The amplitude on the fasting day was 11% higher ( p = 0.224) than the day after. The acrophase advanced on the day of fasting, 48 min earlier than the day before ( p = 0.0064), and by 39 min to the day after fasting ( p = 0.0005). In the rhythm of DHEA, differences were found in the MESOR ( p = 0.0381). The MESOR on the fasting day increased. Discussion Our results obtained during 64 consecutive hours of saliva sampling suggest that one-day fasting may affect three components of cortisol and DHEA daily rhythm. Additionally, no differences were found in the daily rhythm between the morning and evening chronotypes and between females and males. Although aging did not influence daily cortisol rhythm, DHEA amplitude, MESOR, and acrophase changed with age. To the best of our knowledge, this is the first presentation of changes in DHEA rhythm during one-day fasting.

Background: Peritoneal dialysis induces the inflammatory response within the peritoneal cavity, which contributes to the progressive damage of the peritoneum. Due to close contact of the peritoneal cavity and the intestines, there is the possibility that the visceral disorders can affect the intraperitoneal inflammation during peritoneal dialysis. Objectives: Study of the effect of acute colitis on the intraperitoneal inflammation in conditions of peritoneal dialysis and evaluation of the protective effect of hyaluronan in that scenario. Methods: In rats with the dextran sulphate-induced colitis, 6-h peritoneal dialysis was performed with dianeal 2.5% +/− hyaluronan 10 mg/dL. In the control group, rats without colitis were studied. Peritoneal permeability and dialysate inflammation were studied at the end of the dialysate exchange. Results: In rats with colitis, intraperitoneal inflammatory reaction was increased as compared with the control group and reflected by the following studied parameters: dialysate cell count (+26%, p < 0.01), number of neutrophils (+75%, p < 0.01), generation of free radicals in the leukocytes (+70%, p < 0.05), dialysate level of elastase (+102%, p < 0.01), tumor necrosis factor α (+48%, p < 0.01) and monocyte chemoattractant protein-1 (+42%, p < 0.01). Drained dialysate volume was lower (−21%, p < 0.01) and peritoneal permeability increased in rats with colitis (+55%, p < 0.01). In animals with the hyaluronan supplemented dialysis fluids, the intensity of the intraperitoneal inflammation was reduced. Conclusions: Visceral inflammation during colitis induces the inflammatory reaction within the peritoneal cavity that may accelerate damage to the peritoneum. Supplementation of the dialysis fluid with hyaluronan reduces the intensity of that effect.

The aim of our study was to explore if changes in long non-coding RNAs (lncRNAs) expression during pulmonary exacerbation correlate with the immune responses peripherally or in the airways of cystic fibrosis (CF) pediatric patients. Based on previously performed gene expression microarrays analysis, we selected four lncRNAs: lnc-PPP4R1-8, lnc-SLC44A5-1, lnc-MRC2-1, lnc-SERPINA12-1 for quantitative PCR expression study. Whole blood and sputum cell pellets were collected from CF pediatric patients during exacerbation and remission. We also used sputum supernatant from 12 CF patients (6 during PE and 6 in remission) to analyse the expression of selected lncRNAs in sputum-derived extracellular vesicles (EV). RNA was extracted from whole blood, sputum cell pellet, and precipitated EV. Differential gene expression analysis was done using ddCT method in MedCalc statistical software. We found that lnc-SERPINA12-1 showed significantly higher expression in sputum than in peripheral blood (p<0.05). Other lncRNAs were not differentially expressed between blood and sputum. All investigated lncRNAs were present in EV. This lnc-SERPINA12-1 showed the greatest difference between PE and remission, but without statistical significance (p>0.05). According to the literature, lnc-SERPINA12-1 is antisense of the SERPINA12 gene encoding Vaspin that exerts an anti-inflammatory effect. Conclusions: Higher expression of lnc-SERPINA12-1 in sputum indicate increased chronic inflammatory responses in the airways of CF patients, and its presence in EV suggests that it may participate in mediating the local inflammatory effect. The study was supported by the Polish National Science Centre, grant no. 2016/22/E/NZ5/00383 (A. Szczepankiewicz).

The aim of our study was to verify if extracellular vesicles (EVs)-derived miRNAs are associated with pulmonary exacerbation (PE) in the airways of cystic fibrosis (CF) children. We used 24 sputum and 11 exhaled breath condensate (EBC) CF samples and 4 EBC samples from control subjects. MiRNA expression profile was assessed using next-generation sequencing and differential analysis was done using BaseSpace application “Small RNA” and verified with DESeq2 (Bioconductor). Data were normalized and used for the search of miRNAs with the greatest potential for PE differentiation, as well as the best endogenous control for future studies in sputum (Statistica and Normfinder). Differential analysis in both sputum and EBC did not identify any miRNA that significantly distinguished PE from the stable condition in CF patients. Based on normalized expression and DESeq results, we established a very small number of EBC-derived miRNAs that passed the quality filtering, with the highest expression for hsa-miR-767-3p. The comparison of miRNA expression between EBC from CF and control children did not reveal any significantly altered miRNAs. In sputum samples, hsa-let-7b-5p and hsa-miR-26a-5p were the best endogenous controls. The interindividual differences between CF samples, that result from high diversity and heterogeneity of the disease, limit the identification of miRNAs involved in the airway inflammation in CF children. Further efforts to optimize the isolation of EVs, particularly from EBC samples, will be useful to understand the mechanisms responsible for the course of PE. The study was supported by the Polish National Science Centre, grant no. 2016/22/E/NZ5/00383 (A. Szczepankiewicz).

Evaluation of the effects of the drugs used for iron supplementation on the peritoneal mesothelial cells.

Deficiency of a soluble form of the advanced glycation end products receptor (sRAGE) is implicated in obesity-induced complications. Serum sRAGE is inclined to be modified by changes in body weight. We analysed serum sRAGE concentrations in patients with obesity undergoing moderate calorie restriction, which mimics the real-life situation and is not harmful to obese humans. Serum sRAGE was measured by immunoassay in 50 patients with obesity who underwent calorie restriction by 300-500 kcal/day for 8 weeks. In effect calorie restriction resulted in an expected decrease in body weight (by 2.1 kg for an 8-week intervention, p<0.0001), as well as reduced systolic blood pressure, modified dyslipidemia (cholesterol, triglycerides), reduced obesity-related inflammation (tumor necrosis factor-alfa, interleukin-6, C-reactive protein), improved insulin sensitivity. However, it was not accompanied by any significant change in sRAGE concentration. There was a strong negative correlation between BMI and the sRAGE level. Accordingly, the levels of sRAGE were the highest in lean control. In conclusion: a modest weight reduction is unlikely to improve decreased sRAGE levels.

Context: Flaxseed has a characteristic fatty acids composition and unique phytonutrient profile that may have health-promoting properties. Objective: This study aimed to determine the effects of 10 weeks of supplementation with the flaxseed (28 g/day) on endothelial cells (EC) function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. Materials and methods: Eleven lean patients with severe dyslipidaemia treated with apheresis (group 1; 10 weeks treated in four phases: (i) ordinary diet, (ii) ordinary diet + flaxseed, (iii) ordinary diet (wash out), (iv) ordinary diet + placebo) and eleven obese patients with mild dyslipidaemia-not treated with apheresis (group 2; 10 weeks treated in two phases: (i) ordinary diet, (ii) low fat diet + flaxseed). Flaxseed was given blindly. Serum was collected at the end of each phase of the study. ECs were exposed in vitro to the medium supplemented with pooled serum taken from patients from both groups to detect their morphological changes using light and electron microscopy. ECs proliferation was also measured at the end of each study phase. Results: Serum vascular endothelial growth factor was decreased after flaxseed supplementation but only in group 1. ECs proliferation was increased after flaxseed supplementation only in obese patients. ECs exposed to medium supplemented with obese patients' serum revealed the following cellular abnormalities: accumulation of lipid droplets, changes of rough endoplasmic reticulum and mitochondria, and flaxseed did not reverse observed changes. At the same time, flaxseed supplementation decreases total cholesterol in both tested groups, low-density lipoprotein cholesterol in group 1 and triglycerides in group 2. Conclusions: Our findings support the potential role of flaxseed in treating dyslipidaemia but indicate only a slight impact on endothelial cell function.