Hepatitis C virus cell entry : role of lipoproteins and cellular receptors

Hepatitis C virus (HCV), a major cause of chronic liver disease, is a single-stranded positive sense virus of the family Flaviviridae. HCV cell entry is a multi-step process, involving several viral and cellular factors that trigger virus uptake into the hepatocyte. Tetraspanin CD81, human scavenger receptor SR-BI, and tight junction molecules Claudin-1 and occludin are the main receptors that mediate HCV entry. In addition, the virus may use glycosaminoglycans and/or low density receptors on host cells as initial attachment factors. A unique feature of HCV is the dependence of virus replication and assembly on host cell lipid metabolism. Most notably, during HCV assembly and release from the infected cells, virus particles associate with lipids and very-low-density lipoproteins. Thus, infectious virus circulates in patient sera in the form of triglyceride-rich particles. Consequently, lipoproteins and lipoprotein receptors play an essential role in virus uptake and the initiation of infection. This review summarizes the current knowledge about HCV receptors, mechanisms of HCV cell entry and the role of lipoproteins in this process

Verbal Fluency in a Speech Assessment. Comparative Studies in the Group of Young People and the Senioral Age

The article describes the issue of verbal fluency which is perceived in the field of speech therapy as an important component of assessment in many units of speech pathology. The author presented the results of his own research conducted in a group of 40 young people and elderly people, using our own procedure including 8 trials of various trials: oral and written, regarding semantic and literal fluency. Presenting the results of comparative, quantitative and qualitative analysis, within the examined categories, it took into account the number of correctly generated words, the number and diversity of clusters, paying attention to the specificity of the lexical resource in the context of the biolect, and the number of errors made. In addition, to recognize the strategies used by the respondents during the tasks and ways of dealing with difficulties with generating words were identified. The procedure developed for the purposes of own research, which included various types of samples, allowed for more details of verbal fluency assessment, and showed the diversity of the studied groups in the defined range of phenomena.Artykuł poświęcony jest zagadnieniu fluencji słownej, postrzeganej na gruncie logopedii jako ważny komponent oceny w wielu jednostkach patologii mowy. Autorka przedstawiła wyniki badań własnych przeprowadzonych w grupie 40 osób młodych i osób w wieku senioralnym, z zastosowaniem własnej procedury, obejmujących osiem zróżnicowanych prób: ustnych i pisemnych, dotyczących fluencji semantycznej oraz literowej. Prezentując wyniki analizy porównawczej, ilościowej i jakościowej, w ramach badanych kategorii uwzględniła liczbę poprawnie generowanych słów oraz liczbę i zróżnicowanie klastrów, ze zwróceniem uwagi na specyfikę zasobu leksykalnego w kontekście biolektu, a także liczbę popełnionych błędów. Dodatkowo rozpoznała strategie stosowane przez badanych podczas wykonywania zadań i sposoby radzenia sobie z trudnościami z generowaniem słów. Opracowana na potrzeby badań własnych procedura, obejmująca różnorodne rodzaje prób, pozwoliła uszczegółowić ocenę fluencji słownej i pokazać odmienność badanych grup w wyznaczonym zakresie zjawisk

Jaka jest „idealna matka”? Rozumienie roli matki przez współczesne kobiety

The aim of the study was to answer the question of how contemporary Polish women understand the role of mother and how this understanding refers to a theoretical model defined by Maria Ziemska. For this purpose, 35 indicators of parental attitudes were specified and then, reference to the discourses on motherhood publicized on the Internet through six blogs written by contemporary mothers, was made. Thanks to conducted analysis of maternal experience (published during one year), there were diagnosed not only the current reinterpretation of the ideas of perfect mother, but also the diversity of present-day parental attitudes of Polish women. Interpretation of results was based on Interpretative Phenomenological Analysis.W niniejszym opracowaniu autorki próbują udzielić odpowiedzi na pytanie, jak współczesne Polki rozumieją rolę matki i czy to rozumienie odnosi się do teoretycznego modelu idealnej/dobrej matki określonego przez M. Ziemską. W tym celu wyszczególniono 35 wskaźników postaw rodzicielskich, po czym odniesiono się do internetowych dyskursów na temat macierzyństwa upublicznionych za pośrednictwem sześciu blogów prowadzonych przez współczesne matki. Dzięki przeprowadzonej analizie doświadczeń macierzyńskich (opublikowanych w ciągu roku) rozpoznano nie tylko aktualną reinterpretację wyobrażeń o matce idealnej, ale także różnorodność postaw rodzicielskich typowych dla współczesnych Polek. Interpretacji wyników dokonano w oparciu o Interpretacyjną Analizę Fenomenologiczną

Evidence of stem cells mobilization in the blood of patients with pancreatitis : a potential link with disease severity

A growing number of studies indicate the potential involvement of various populations of bone marrow-derived stem cells (BMSCs) in tissue repair. However, the mobilization of BMSCs to the peripheral blood (PB) in acute and chronic pancreatitis (AP and CP) has not been investigated. A total of 78 patients were assigned into AP, CP, and healthy control groups in this study. Using flow cytometry, we found that VSELs, EPCs, and $CD133^{+}SCs$ were mobilized to the PB of patients with both AP and CP. Interestingly, AP and CP patients exhibited lower absolute number of circulating MSCs in the PB compared to healthy individuals. SC mobilization to the PB was more evident in patients with AP than CP and in patients with moderate/severe AP than mild AP. Using ELISA, we found a significantly increased HGF concentration in the PB of patients with AP and $SDF1\alpha$ in the PB of patients with CP. We noted a significant positive correlation between $SDF1\alpha$ concentration and the mobilized population of $CD133^{+}SCs$ in AP and between C5a and the mobilized population of VSELs moderate/severe AP. Thus, bone marrow-derived SCs may play a role in the regeneration of pancreatic tissue in both AP and CP, and mobilization of VSELs to the PB depends on the severity of AP

Identification of a Functional, CRM-1-Dependent Nuclear Export Signal in Hepatitis C Virus Core Protein

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified

An intensified systemic trafficking of bone marrow-derived stem/progenitor cells in patients with pancreatic cancer

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

Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection.

International audienceHepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the inhibition of virus-cell fusion and thus HCV cell entry. Therefore besides other beneficial roles, ABCA1 might represent a potential target for HCV therapy

Assessment of Complement Cascade Components in Patients With Bipolar Disorder

Introduction: The immune system is undoubtedly involved in the pathogenesis of various psychiatric disorders, such as schizophrenia, bipolar disorder, or depression. Although its role is not fully understood, it appears that this area of research can help to understand the etiology of mental illness. One of the components of the human immune system is the complement system, which forms a part of the innate immune response. Physiologically, except for its essential protective role, it is a vital element in the regeneration processes, including neurogenesis. To date, few studies have tried to clarify the role of the complement cascade in mental disorders.Materials and Methods: We evaluated concentrations of C3a, C5a, and C5b-9 complement cascade components in the peripheral blood of 30 patients suffering from bipolar disorder (BD) for at least 10 years, in euthymia, who were not treated with lithium salts. In addition, we divided our study sample into BD type I (BD-I, 22 persons), and BD type II (BD-II, 8 patients). The control group consisted of 30 healthy volunteers matched for age, sex, BMI, and smoking habits.Results: Compared to healthy controls, BD patients had elevated concentrations of all the investigated components. Furthermore, in patients with BD-II, we observed higher concentrations of C5b-9 as compared to patients with BD-I. However, there was a significant effect of BD diagnosis only on the levels of C3a and C5a but not on the level of C5b-9 after adjustment for potential confounding factors.Conclusions: Increased concentrations of components C3a and C5a of the complement system in the investigated group as compared to healthy controls suggest involvement of the complement cascade in the pathogenesis of BD, and provides further evidence of immune system dysregulation in BD patients