The role of blood proteinases in the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not well understood. As previously reported, activation of the complement cascade (ComC) and cleavage of C5 by C5 convertase are enabling events in the release of C5a that plays a crucial role in the egress of HSPCs from bone marrow (BM) into peripheral blood (PB) and explains why C5-deficient mice are poor mobilizers. Here we provide evidence that during granulocyte colony-stimulating factor- and AMD3100-induced mobilization, not only the ComC but also two other evolutionarily ancient proteolytic enzyme cascades, the coagulation cascade (CoaC) and the fibrynolytic cascade (FibC), become activated. Activation of all three cascades was measured by generation of C5a, decrease in prothrombin time and activated partial thromboplastin time as well as an increase in the concentrations of plasmin/antiplasmin and thrombin/antithrombin. More importantly, the CoaC and FibC, by generating thrombin and plasmin, respectively, provide C5 convertase activity, explaining why mobilization of HSPCs in C3-deficient mice, which do not generate ComC-generated C5a convertase, is not impaired. Our observations shed more light on how the CoaC and FibC modulate stem cell mobilization and may lead to the development of more efficient mobilization strategies in poor mobilizers. Furthermore, as it is known that all these cascades are activated in all the situations in which HSPCs are mobilized from BM into PB (for example, infections, tissue/organ damage or strenuous exercise) and show a circadian rhythm of activation, they must be involved in both stress-induced and circadian changes in HSPC trafficking in PB.

Fibroblast growth factors (FGF) constitute a large family of proteins with pleiotropic effects on development, organogenesis, and metabolism. The FGF19 subclass includes growth factors circulating with the blood referred to as endocrine FGF. Representatives of the FGF19 subclass, including FGF19, FGF21, and FGF23, act via FGFR receptors. The proteins of FGF19 subfamily influence the enterohepatic circulation of bile, participate in glucose and lipid metabolism regulation, and maintenance of phosphorus and vitamin D3 homeostasis. FGF19 and FGF21 are activated under different physiological and pathological conditions.

a b s t r a c tSystemic cryostimulation is useful treatment, both in sport and medicine, during which human body is exposed to very low, cryogenic temperature (below À100°C). Although there exists some evidence of its beneficial effect in biological regeneration, so far it has not been unequivocally determined if the positive effect of repeated stimulations depends on their number in a series. The aim of this research was to estimate the influence of 5, 10 and 20 sessions of 3 min-long exposures to cryogenic temperature (À130°C) on the lipid profile in physically active men. Sixty-nine healthy volunteers participated in the study. The blood samples were taken in the morning, after overnight fasting, before the first cryostimulation session, and the following morning after the last one (5th,10th, 20th).In serum specimens the concentration of total cholesterol (TCh), HDL cholesterol and triglicerydes were determined using enzymatic methods. LDL cholesterol level was calculated using Friedewald formula. The changes in lipid profile (LDL decrease with simultaneously HDL increase) occurred after at least 10 sessions of cryostimulation.Ó 2010 Elsevier Inc. All rights reserved. IntroductionWhole-body cryostimulation in a cryogenic chamber uses very low temperatures (ranging from À100 to À160°C) over a short time span (1-3 min) to induce systemic physiological responses. It is based on the heat exchange between surfaces with different temperatures [30]. Heat is absorbed by cooled surface tissues from deeper situated tissues at the rate proportional to their difference in temperature.A desired response to a systemic effect of cryogenic temperatures (below À100°C) is a hyperaemic reaction (rebound effect), stimulatory in character. Exposure in cryogenic chamber, under a supervision of a physician and in compliance to commonly accepted rules concerning cryostimulation, is not harmful or dangerous to healthy individuals, although there exist several contraindications. Banfi et al. reported that whole-body cryotherapy is not deleterious to cardiac function in healthy individuals [1]. Documented analgesic, anti-inflammatory and antioedematous action reduces increased muscle tension and therefore cryotherapy has been increasingly often applied in sport and medicine, in combination with additional forms of treatment [13,14,25,34,36].It is postulated that cryostimulation mobilizes the white blood cells, particularly immunocompetent lymphocytes [4,15,21,22]. The effect on red blood cells has not been positively confirmed. Banfi et al. did not observe changes in the level of hematocrit, whereas red blood cells and mean corpuscular hemoglobin decreased after 5 cryostimulation sessions [2,3]. On the contrary, significant increase in erythrocytes count, hemoglobin concentration, hematocrit value and the mean corpuscular value (MCV) were reported by Stanek et al. [33].It is unclear how repeated cryostimulation influences the level of pro-inflammatory and anti-inflammatory mechanisms. There is a report of increased anti-inflammatory cy...

Heavy metals may exacerbate metabolic syndrome (MS) but abnormal serum concentrations of bioelements may also co-exist with MS. The primary aim of the study was to assess the relationship of blood heavy metal and bioelement concentrations and MS, in men aged 50–75 years. Heavy metals—lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), tungsten (W), Macroelements—magnesium (Mg) and calcium (Ca), and microelements—iron (Fe), zinc (Zn) copper (Cu), chromium (Cr), molybdenum (Mo), selenium (Se) and manganese (Mn), body mass index (BMI), waist to hip ratio (WHR), abdominal circumference (AC) and blood pressure (BP), total cholesterol (TCh), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), fasting plasma glucose (FPG), insulin, and Homeostasis Model Assessment—Insulin resistance (HOMA-IR). The men with MS showed statistically significant higher Zn and lower Mg concentrations. Those with diabetes had higher Ca concentration and lower Mg concentration. Cr and Mn concentrations were significantly higher in obese men. The participants with hypertension had lower Mg concentration. We found statistically significant positive correlations (W-TCh, W-LDL, Mg-TCh, Mg-LDL, Ca-TCh, Ca-LDL, Ca-insulin, Ca-HOMAR-IR, Zn-TG, Zn-insulin, Zn-HOMA-IR, Cu-BP systolic, Mn-BMI, Mn-AC, Mn-WHR, Mn-insulin, Mn-HOMA-IR, Se-TCh, Se-LDL, Se-TG, Se-insulin, Se-HOMA-IR, Cr-TCh, Cr-HDL, Cr-LDL, Cr-TG) and negative correlations (Cd-insulin, Hg-WHR, W-insulin, W-HOMA-IR, Mg-BMI, Mg-AC, Mg-WHR, Mg-BP systolic, Mo-insulin, Mn-HDL). Tungsten may contribute to lipid disorders. Magnesium appears to play the protective role in the occurrence of metabolic disorders. Microelements Mn, Cr and Se may intensify MS.

Various experimental studies indicate potential involvement of bone marrow (BM)-derived stem cells (SCs) in malignancy development and progression. In this study, we comprehensively analysed systemic trafficking of various populations of BM-derived SCs (BMSCs), i.e., mesenchymal, haematopoietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), and of recently discovered population of very small embryonic/epiblast-like SCs (VSELs) in pancreatic cancer patients. Circulating CD133+/Lin−/CD45−/CD34+ cells enriched for HSCs, CD105+/STRO-1+/CD45− cells enriched for MSCs, CD34+/KDR+/CD31+/CD45− cells enriched for EPCs and small CXCR4+CD34+CD133+ subsets of Lin−CD45− cells that correspond to VSELs were enumerated and sorted from blood samples derived from 29 patients with pancreatic cancer, and 19 healthy controls. In addition, plasma levels of stromal-derived factor-1 (SDF-1), growth/inhibitory factors and sphingosine-1-phosphate (S1P; chemoattractants for SCs), as well as, of complement cascade (CC) molecules (C3a, C5a and C5b-9/membrane attack complex – MAC) were measured. Higher numbers of circulating VSELs and MSCs were detected in pancreatic cancer patients (P < 0.05 and 0.01 respectively). This trafficking of BMSCs was associated with significantly elevated C5a (P < 0.05) and C5b-9/MAC (P < 0.005) levels together with S1P concentrations detected in plasma of cancer patients, and seemed to be executed in a SDF-1 independent manner. In conclusion, we demonstrated that in patients with pancreatic cancer, intensified peripheral trafficking of selected populations of BMSCs occurs. This phenomenon seems to correlate with systemic activation of the CC, hepatocyte growth factor and S1P levels. In contrast to previous studies, we demonstrate herein that systemic SDF-1 levels do not seem to be linked with increased mobilization of stem cells in patients with pancreatic cancer.

It is claimed that WBC (whole-body cryotherapy) enhances the resistance of the human body, also thanks to the beneficial effect on the antioxidant system. Accordingly, this research aimed to evaluate the effect of a series of whole-body cryostimulations on the level of non-enzymatic antioxidants and the activity of antioxidant enzymes in healthy men. The study was carried out on 30 young and healthy men aged 27.8±6.1 years with average body mass index and peak oxygen consumption (46.34±6.15 ml kg−1 •min−1). The participants were daily exposed for 3 minutes to cryogenic temperatures (−130°C). Blood samples were obtained in the morning before cryostimulation, again 30 min after exposure and the following day in the morning, during the 1st, 10th and 20th session. Analysis concerned changes in plasma concentrations of total protein, albumin, glucose, uric acid and ceruloplasmin, and the most important components of the antioxidant system in red blood cells: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced and oxidized glutathione. To assess the oxidative stress level the 8-isoprostane concentration in plasma was measured. The obtained results indicate that cryogenic temperatures in repeated daily treatments result in changes in the peroxidant and antioxidant status. These changes seem to depend on the number of cryostimulations. After 20 daily treatments there was an increase in SOD, SOD:CAT ratio, a decrease in the concentration of reduced and oxidized glutathione and in the activity of GPx. It could be possible that differences in the activity of GSSG-R after 20 treatments depended on the body mass index of participants.

The aim of this study was to determine the effect of six-month-long physical exercise programme with a two-time exposure to whole-body cryostimulation (WBC) in 20 sessions on antioxidant enzyme activities, lipid profile, and body composition changes in obese people (30 adult subjects; BMI = 30.39 ± 4.31 kg/m2). Blood samples were taken before the programme, one month following the exercise programme, before and after the first WBC treatment, six months following the exercise programme, after the second WBC treatment, and finally one month after the intervention. Six months of moderate aerobic activity combined with WBC did not change body mass or fat and lean body mass percentages, or circulating adiponectin, leptin, and resistin concentrations. In response to intervention a significant decrease in the level of low-density lipoprotein and triglycerides was observed, with a slight increase in high-density lipoprotein concentration. The nature of changes in the activity of respective antioxidant enzymes was not identical. After one month of increased physical activity, a significant decrease in superoxide dismutase, catalase, and glutathione reductase activities was observed (13%, 8%, and 70%, resp.). The SOD activity increased significantly after successive whole-body cryostimulation sessions. As regards catalase, a significant progressive decrease in its activity was observed.

Background/AimsRecent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting.MethodsIn this study, we examined the levels of a broad panel of cytokines, including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα) and granulocyte-colony stimulating factor (G-CSF) in patients with pancreatic adenocarcinoma (n = 43), other pancreatic malignancies (neuroendocrine [n = 10] and solid pseudopapillary tumors [n = 3]), and healthy individuals (n = 41).ResultsWe found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p<0.03). Cancer patients had lower IL-23 concentrations than healthy individuals and patients diagnosed with other types of malignancies (for both, p = 0.002). Levels of IL-6, IL-8, IL-10, and IL-23 were significantly associated with the direct number of circulating bone marrow (BM)-derived mesenchymal or very small embryonic/epiblast-like stem cells (SCs) in patients with pancreatic cancer. Moreover, our study identified a potential ability of IL-6, IL-8, IL-10, IL-23, and TNFα levels to enable discrimination of pancreatic cancer from other pancreatic tumors and diseases, including acute and chronic pancreatitis and post-pancreatitis cysts (with sensitivity and specificity ranging between 70%–82%).ConclusionsOur study i) supports the significance of selected cytokines in the clinical presentation of pancreatic cancer, ii) highlights numerous associations between selected interleukins and intensified BMSCs trafficking in patients with pancreatic cancer, and iii) preliminarily characterizes the diagnostic potential of several cytokines as potential novel clinical markers of pancreatic cancer in humans.