Izabela Kubiszewska

Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Pediatric Helicobacter pylori Infection and Circulating T-Lymphocyte Activation and Differentiation

Background:  In this study, H. pylori‐infected and noninfected children with gastritis were compared to a control group with respect to circulating CD4+ and CD8+ T lymphocytes expressing activation and differentiation markers. Additionally, the lymphocyte phenotypes of children with gastritis were correlated with the gastric inflammation scores.

Does the liposuction method influence the phenotypic characteristic of human adipose-derived stem cells?

Statistical analysis revealed significant differences in antigen expression of 58 markers of the 242 studied. The method of liposuction has no significant impact on antigens profile in cultured ASCs (adipose-derived stem cells).

Lactic acid bacteria strains exert immunostimulatory effect on H. pylori-induced dendritic cells.

The aim of this study was to find out if selected lactic acid bacteria (LAB) strains (antagonistic or nonantagonistic against H. pylori in vitro) would differ in their abilities to modulate the DCs maturation profiles reflected by their phenotype and cytokine expression patterns. Methods. Monocyte-derived DCs maturation was elicited by their direct exposure to the LAB strains of L. rhamnosus 900 or L. paracasei 915 (antagonistic and nonantagonistic to H. pylori, resp.), in the presence or absence of H. pylori strain cagA+. The DCs maturation profile was assessed on the basis of surface markers expression and cytokines production. Results. We observed that the LAB strains and the mixtures of LAB with H. pylori are able to induce mature DCs. At the same time, the L. paracasei 915 leads to high IL-10/IL-12p70 cytokine ratio, in contrast to L. rhamnosus 900. Conclusions. This study showed that the analyzed lactobacilli strains are more potent stimulators of DC maturation than H. pylori. Interestingly from the two chosen LAB strains the antagonistic to H. pylori-L. rhamnosus strain 900 has more proinflammatory and probably antibactericidal properties.

Expression of Adiponectin Receptors on Peripheral Blood Leukocytes of Hypertensive Children Is Associated with the Severity of Hypertension

The aim of the study was to find out whether peripheral blood leukocyte adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) protein expression patterns (flow cytometry) differ between the primary hypertension children (n = 57) and healthy controls (n = 19) and if their expression levels are related to selected clinical parameters. The group of 26 patients [AdipoR(−)] showed lower and the group of 31 patients [AdipoR(+)] showed higher AdipoRs protein expression than the control and each other (P < 0.01 for neutrophils, P < 0.05 for monocytes). The AdipoR(+) leukocytes expressed higher AdipoR1 mRNA levels (RT-PCR) than AdipoR(−) ones and controls (P = 0.022 and P = 0.007, resp.). Despite greater BMI, the AdipoR(−) patients had unchanged serum adiponectin levels. In contrast, AdipoR(+) patients had lower serum adiponectin concentrations than the AdipoR(−) ones and controls (P < 0.001). The AdipoR(+) patients had higher blood pressure (P = 0.042) and greater carotid intima-media thickness (P = 0.017) than the AdipoR(−) ones. The stage of hypertension was associated with increased neutrophil but not monocyte AdipoR1 density (AdipoR1 MFI) (P < 0.05). Severe ambulatory hypertension was presented more often in AdipoR(+) patients than in AdipoR(−) ones (51.6% versus 26.9%, resp.; P < 0.01). In conclusion, neutrophil AdipoRs upregulation was associated with early stages of vascular injury, hypertension severity, and low serum levels of adiponectin.

Altered matrix metalloproteinase 9 and tissue inhibitor of metalloproteinases 1 levels in children with primary hypertension

Background: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are involved in cardiovascular remodeling in hypertension. Because metabolic abnormalities typical of metabolic syndrome is the dominant phenotype of primary hypertension in children, we hypothesized that MMP-9 and TIMP-1 plasma concentrations are altered in hypertensive children and correlate with metabolic abnormalities and target organ damage. Method: A total of 109 children (15.6, 10–17 years) with untreated primary hypertension were included to the study. The control group consisted of 74 healthy, normotensive children. Results: Plasma MMP-9, TIMP-1 concentrations, and MMP-9/TIMP-1 ratio were significantly elevated in hypertensive boys in comparison with normotensive boys (P = 0.0001, P = 0.04, and P = 0.001, respectively), whereas there were no differences between hypertensive and normotensive girls. The levels of MMP-9 and TIMP-1 as well as MMP-9/TIMP-1 ratio were not associated either with hypertension stage, left ventricular hypertrophy, or carotid intima–media thickness. However, in a subgroup of 30 hypertensive patients in whom arterial stiffness was measured, TIMP-1 concentrations correlated with aortic pulse pressure (P < 0.05; r = 0.367), augmentation pressure (P < 0.05; r = 0.428), and augmentation index (P < 0.05; r = 0.404). Only hypertensive boys presented negative correlations of both MMP-9 and TIMP-1 levels with high-density lipoprotein cholesterol (r = −0.254, P = 0.01 and r = −0.241, P = 0.02, respectively). Conclusion: Hypertensive boys but not girls had elevated MMP-9 and TIMP-1 plasma concentrations, which indicates sex-related role of MMP/TIMP system in pediatric hypertension. The correlation between serum TIMP-1 and markers of arterial stiffness indicates on the involvement of TIMPs in arterial remodeling.

Melanoma cell adhesion molecule as an emerging biomarker with prognostic significance in systolic heart failure

BACKGROUND Melanoma cell adhesion molecule (MCAM) is a marker of endothelial damage. MCAM diagnostic and prognostic value was assessed in chronic heart failure (CHF). MATERIALS & METHODS 130 CHF patients and 32 controls were included in the study. Telephone follow-up lasted one year. End points were: death from all causes, and hospitalization with CHF exacerbation. RESULTS MCAM was higher in patients than in controls (p = 0.01). Receiver operator curve analysis revealed that MCAM may serve as a predictor of death (area under the curve: 0.8404; p < 0.002). Patients with MCAM above 500 ng/ml had worse prognosis (p = 0.03). NT-proBNP and age were independent predictors of death in multivariate analysis. CONCLUSION The increased MCAM indicates endothelial damage in CHF and may serve as a marker of worse prognosis in these patients.

Expression of Adhesion and Activation Molecules on Circulating Monocytes in Children with Helicobacter pylori Infection

Objectives:  The aim of this study was to assess the cell surface expression of adhesion (CD11a, CD11b, CD11c, CD18, CD54, and CD58) and activation (CD14, HLA‐DR, and CD16) molecules on the circulating monocytes in Helicobacter pylori (H. pylori)‐infected and noninfected children with gastritis, with the goal of comparing the results with those obtained from the controls.

Cytoskeletal changes during cellular response of the A549 lung cancer cells to continuous cisplatin treatment

The cytoskeleton is a ubiquitous cellular structure that plays a crucial role in most processes of living cells. There are reports suggesting that this system not only reflects, but also contributes to many different processes, including cell death. In this study, we examined alterations of both MT and MF cytoskeletal systems related to cell death, which was induced in A549 cells by continuous cisplatin treatment. We observed that specific changes in these cytoskeletal proteins accompany cell death, while the others are associated with increased repair and cell survival. It seems that the predominant mode of cell death triggered by cisplatin was an apoptotic‐like pathway, but on the other hand, coincidence with some features of necrosis and autophagy was also demonstrated in our conditions.

Evaluation of serum heat shock protein 70 concentration in women with recurrent miscarriages

Atrial fibrillation (AF) is the most common type of arrhythmia. AF increases the risk of thromboembolic complications including stroke. Stroke in patients with AF is more severe compared with patients with sinus rhythm. Long-term oral anticoagulant therapy (OAT) is widely used in a large population of patients with AF to prevent arterial thromboembolic events, such as stroke and systemic embolism. However, it is well established that OAT significantly increases the risk of bleeding. Percutaneous left atrial appendage closure (LAAC) is an option for stroke prophylaxis in patients with nonvalvular AF and high risk of bleeding. This paper provides an overview of recent studies that address the effectiveness and safety of LAAC using the Amplatzer Cardiac Plaque and Watchman Left Atrial Appendage System. LAAC provides a superior choice of treatment in patients with absolute contraindication of systemic OAT, in cases of refusal of systemic OAT by a patient, and as a complementary treatment to anticoagulation in patients with embolic events despite adequate OAT. LAAC should be also considered as a therapeutic option for patients with high thromboembolic risk and very high bleeding risk on the basis of individual risk/benefit evaluation for OAT vs. alternative methods of treatment. In general, LAAC becomes more attractive with increasing thromboembolic risk. There is a need for further studies to address the question of whether LAAC is actually the best method for preventing thromboembolism for patients with moderate/high thromboembolic risk and relatively low bleeding risk, to determine the optimum antithrombotic or antiplatelet therapy in patients who underwent LAAC, as well as to conduct direct comparative analysis of LAAC and the use of new oral anticoagulant drugs (NOAC).