Hepatitis C Virus Infection and Mixed Cryoglobulinemia

Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures

Assessment of total hepatitis C virus (HCV) core protein in HCV-related mixed cryoglobulinemia

INTRODUCTION: In hepatitis C virus (HCV)-related mixed cryoglobulinemia (MCG), the nonenveloped HCV core protein (HCV-Cp) is a constituent of the characteristic cold-precipitating immune complexes (ICs). A possible correlation between HCV-Cp, virologic, laboratory, and clinical parameters in both untreated MCG patients and those undergoing specific treatment was explored. METHODS: HCV-Cp was quantified by a fully automated immune assay. Correlations between HCV-Cp and HCV RNA, cryocrit, and virus genotype (gt) were investigated in 102 chronically HCV-infected MCG patients. RESULTS: HCV-Cp concentrations strongly correlated with HCV RNA levels in baseline samples. An average ratio of 1,425 IU and 12,850 IU HCV RNA per picogram HCV-Cp was estimated in HCV gt-1 and gt-2 patients, respectively. This equation allowed us to estimate that, on average, HCV-Cp was associated with the viral genome in only 3.4% of the former and in 35% of the latter group of patients. The direct relation between HCV-Cp and the cryocrit level suggests that the protein directly influences the amount of cryoprecipitate. Although the therapy with rituximab (RTX) as a single agent resulted in the enhancement of HCV-Cp levels, in patients treated with RTX in combination with a specific antiviral therapy (pegylated interferon-α plus ribavirin), the prompt and effective clearance of HCV-Cp was documented. CONCLUSIONS: Our data provide evidence that HCV-Cp has a direct effect on the cold-precipitation process in a virus genotype-dependence in HCV-related MCG patients

Effect of Feijoa Sellowiana Acetonic Extract on Proliferation Inhibition and Apoptosis Induction in Human Gastric Cancer Cells

Gastric cancer (GC) still represents a relevant health problem in the world for both incidence and mortality rates. Many studies underlined that natural products consumption could reduce GC risk, indicating flavonoids as responsible for the beneficial eects through the modulation of several biological processes, such as the inhibition of cancer antioxidant defense and induction of apoptosis. Since Feijoa sellowiana fruit is known to contain high amounts of flavonoids, among which is flavone, we evaluated the antiproliferative and proapoptotic eects of F. sellowiana acetonic extract on GC cell lines through MTS and Annexin-V FITC assays. Among three GC cell lines tested, SNU-1 results being sensitive to both the F. sellowiana acetonic extract and synthetic flavone, which was used as the reference treatment. Moreover, we evaluated their antioxidant eects, assessing the activity of the antioxidant enzymes supeoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in polymorphonuclear cells. We found a significant increase of their activity after exposure to both F. sellowiana acetonic extract and flavone, supporting the idea that a diet that includes flavone-rich fruits could be of benefit for health. In addition to this antioxidant eect on normal cells, this study indicates, for the first time, an anticancer eect of F. sellowiana acetonic extract in GC cells

Role of IL-6/STAT3 Axis in Resistance to Cisplatin in Gastric Cancers

Gastric cancer, the second most common cause of death worldwide, is characterized by poor prognosis and low responsiveness to chemotherapy. Indeed, multidrug resistance, based mainly on cellular and molecular factors, remains one of the most limiting factors of the current approach to gastric cancer (GC) therapy. We employed a comprehensive gene expression analysis through data mining of publicly available databases to assess the role of the signal transducer and activator of transcription 3 (STAT3) in gastric cancer drug efficiency. It has been proposed that gastric cancer cells are less sensitive to these drugs because they develop resistance to these agents through activating alternative signalling pathways responsible for overcoming pharmacological inhibition. Our study evaluated the hypothesis that activating STAT3 signalling in response to cisplatin reduces the reaction to the drug. Consistent with this hypothesis, inhibition of interleukin 6 (IL-6)/STAT3 in combination therapy with cisplatin prevented both STAT3 activation and more lethality than induction by a single agent. The data suggest that the IL-6/STAT3 axis block associated with cisplatin treatment may represent a strategy to overcome resistance

Gastric Cancer Stem Cells: A Glimpse on Metabolic Reprogramming

Gastric cancer (GC) is one of the most widespread causes of cancer-related death worldwide. Recently, emerging implied that gastric cancer stem cells (GCSCs) play an important role in the initiation and progression of GC. This subpopulation comprises cells with several features, such as self-renewal capability, high proliferating rate, and ability to modify their metabolic program, which allow them to resist current anticancer therapies. Metabolic pathway intermediates play a pivotal role in regulating cell differentiation both in tumorigenesis and during normal development. Thus, the dysregulation of both anabolic and catabolic pathways constitutes a significant opportunity to target GCSCs in order to eradicate the tumor progression. In this review, we discuss the current knowledge about metabolic phenotype that supports GCSC proliferation and we overview the compounds that selectively target metabolic intermediates of CSCs that can be used as a strategy in cancer therapy

“Gli aspetti innovativi dell’informativa finanziaria nelle “entità” del settore pubblico: gli IPSAS 5, 15, 18, 19 e 21”

Per il citato lavoro, che rappresenta un contributo alla ricerca della Scuola Superiore della Pubblica Amministrazione “Principi e metodi di contabilità economico-patrimoniale per lo Stato e le Pubbliche Amministrazioni nel quadro teorico ed operativo internazionale” (coordinatore Prof. L. Anselmi, anni 2007/2008), sono stati assolti gli obblighi di pubblicazione direttamente dall’autore, ai sensi della Legge 15.4.2006 n. 106 e del D.P.R. 03.05.2006, n. 252

One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages

The COVID-19 pandemic was officially declared on March 11th, 2020. Since the very beginning, the spread of the virus has been tracked nearly in real-time by worldwide genome sequencing efforts. As of March 2021, more than 830,000 SARS-CoV-2 genomes have been uploaded in GISAID and this wealth of data allowed researchers to study the evolution of SARS-CoV-2 during this first pandemic year. In parallel, nomenclatures systems, often with poor consistency among each other, have been developed to designate emerging viral lineages. Despite general fears that the virus might mutate to become more virulent or transmissible, SARS-CoV-2 genetic diversity has remained relatively low during the first ~ 8 months of sustained human-to-human transmission. At the end of 2020/beginning of 2021, though, some alarming events started to raise concerns of possible changes in the evolutionary trajectory of the virus. Specifically, three new viral variants associated with extensive transmission have been described as variants of concern (VOC). These variants were first reported in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Their designation as VOCs was determined by an increase of local cases and by the high number of amino acid substitutions harboured by these lineages. This latter feature is reminiscent of viral sequences isolated from immunocompromised patients with long-term infection, suggesting a possible causal link. Here we review the events that led to the identification of these lineages, as well as emerging data concerning their possible implications for viral phenotypes, reinfection risk, vaccine efficiency and epidemic potential. Most of the available evidence is, to date, provisional, but still represents a starting point to uncover the potential threat posed by the VOCs. We also stress that genomic surveillance must be strengthened, especially in the wake of the vaccination campaigns

Gastric Normal Adjacent Mucosa Versus Healthy and Cancer Tissues: Distinctive Transcriptomic Profiles and Biological Features

Gastric cancer (GC) is a leading cause of cancer-related deaths in the world. Molecular heterogeneity is a major determinant for the clinical outcomes and an exhaustive tumor classification is currently missing. Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies, nevertheless a recently published paper described the unique characteristics of the NAT in several tumor types. Little is known about the global gene expression profile of gastric NAT (gNAT) which could be an effective tool for a more realistic definition of GC molecular signature. Here, we integrated data of 512 samples from the Genotype-Tissue Expression project (GETx) and The Cancer Genome Atlas (TCGA) to analyze the transcriptome of healthy gastric tissues, gNAT, and GC samples. We validated TCGA-GETx data mining through inHouse gNAT and GC expression dataset. Differential gene expression together with pathway enrichment analyses, indeed, led to different results when using the gNAT or the healthy tissue as control. Based on our analyses, gNAT showed a peculiar gene signature and biological features, like the estrogen receptor pathways activation, suggesting a molecular behavior partially different from both healthy and GC tissues. Therefore, using gNAT as healthy control tissue in the characterization of tumor associated biological processes and pathways could lead to suboptimal results

Hepatitis C virus-associated B-cell non-Hodgkin's lymphoma: clinical and therapeutic challenges

Hepatitis C virus (HCV) is a major cause of liver-related morbidity and is strongly associated with B cell lymphoproliferative disorders. Data from epidemiological, biological and clinical investigations support the hypothesis of a pathogenetic role of HCV in at least a subgroup of patients with B-cell non-Hodgkin's lymphoma (B-NHL). Morphologically, HCV-associated B-NHL represents a variety of histological subtypes. The comprehension of the mechanisms of HCV persistence and of its role in the lymphomagenesis will be useful to set new strategies with the aim to prevent and treat HCV-associated B-NHLs. This hypothesis of a virus-induced mechanism of lymphomagenesis arises from the growing evidence that successful antiviral treatment is often linked to regression of some types of HCV-related indolent B-NHLs