Farnesoid X receptor alpha ligands inhibit HDV in vitro replication and virion infectivity.

Background And Aims: HDV, a satellite of HBV, is responsible for the most severe form of human viral hepatitis, for which curative therapy is still awaited. Both HBV and HDV use the hepatic transporter of bile acids (ie, Na+-taurocholate cotransporting polypeptide) to enter hepatocytes. We have previously shown that ligands of the farnesoid-X-receptor alpha (FXR), a master regulator of bile acids metabolism, inhibit HBV replication.

Changing epidemiology of hepatitis C in Italy: a population-based survey in a historically high endemic area.

Background: General population data on hepatitis C virus (HCV) prevalence in Italy come mostly from studies conducted in small towns. The highest rates have consistently been found in southern regions, especially in Calabria. Herein, we aimed to determine HCV prevalence, awareness, and risk factors in the general population of Catanzaro, the capital city of Calabria, Italy.

Restoration of RNA helicase DDX5 suppresses hepatitis B virus (HBV) biosynthesis and Wnt signaling in HBV-related hepatocellular carcinoma.

RNA helicase DDX5 is downregulated during hepatitis B virus (HBV) replication, and poor prognosis HBV-related hepatocellular carcinoma (HCC). The aim of this study is to determine the mechanism and significance of DDX5 downregulation for HBV-driven HCC, and identify biologics to prevent DDX5 downregulation. Molecular approaches including immunoblotting, qRT-PCR, luciferase transfections, hepatosphere assays, Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), and RNA-seq were used with cellular models of HBV replication, HBV infection, and HBV-related liver tumors, as well as bioinformatic analyses of liver cancer cells from two independent cohorts.

Generation and testing of engineered multimeric Fabs of trastuzumab.

Recombinant antibodies fragments in several new formats are routinely investigated and used in diagnostic and therapeutic applications as anti-cancers molecules. New antibody formats are generated to compensate the need for multispecificity and site-specific introduction of fluorescent dyes, cytotoxic payloads or for generating semisynthetic multimeric molecules. Fabs of trastuzumab bearing transglutaminase (MTG) reactive sites were generated by periplasmic expression in E.

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes.

Background: A link between HBV and PLK1 was clearly evidenced in HBV-driven carcinogenesis, and we have also recently shown that PLK1 is a proviral factor in the early phases of HBV infection. Moreover, we have shown that BI-2536, a small molecule PLK1 inhibitor, was very efficient at inhibiting HBV DNA neosynthesis, notably by affecting nucleocapsid assembly as a result of the modulation of HBc phosphorylation. Yet, as small molecule kinase inhibitors often feature poor selectivity, a more specific and safer strategy to target PLK1 would be needed for a potential development against chronic HBV infections.

Evidence for swine and human papillomavirus in pig slurry in Italy.

Aims: The diversity and the geographical distribution of swine papillomaviruses (PVs) are virtually unknown. The occurrence and the diversity of swine PV were therefore investigated in pig slurry collected in Italy, to contribute towards filling this gap in knowledge.

Methods And Results: Twenty-two slurry samples underwent analysis by nested PCR and DNA sequencing using published and newly designed specific primer pairs for Sus scrofa papillomavirus (SsPV) type 1 and 2 (SsPV1 and 2), along with degenerate PV-specific primers targeting the major coat protein L1 and the helicase protein E1.

Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro.

Human Cripto-1 (Cripto-1), the founding member of the EGF-CFC superfamily, is a key regulator of many processes during embryonic development and oncogenesis. Cripto-1 is barely present or even absent in normal adult tissues while it is aberrantly re-expressed in various tumors. Blockade of the CFC domain-mediated Cripto-1 functions is acknowledged as a promising therapeutic intervention point to inhibit the tumorigenic activity of the protein.

Discussion on critical points for a tailored therapy to cure hepatitis C virus infection.

Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations.

Synergistic and antagonistic effects of distilled extract and its major components on drug resistant clinical isolates.

In this study we determine the antimicrobial activities of distilled extract and compounds isolated from such extract against clinical MDR strains. The activity of these substances were tested using a broth microdilution assay, their MBC and their FBC to evaluate the nature of the interactions in tested components. Among Gram negative bacteria and exhibited the higher MBC values range (2.

Identification of human papillomavirus type 16 variants circulating in the Calabria region by sequencing and phylogenetic analysis of HPV16 from cervical smears.

Sequence analysis of HPV16 isolates reveals the presence of genome variants with characteristic mutations. The HPV16 variants have different geographical distribution and diverge into four phylogenetic lineages (A, B, C and D) and 16 sub-lineages: A1, A2, A3 (previously known as European variants), A4 (Asian variant), B1, B2, B3, B4, C1, C2, C3, and C4 (African variants), D1 (North-American variant), D2, D3 (Asian-American variants) and D4. Population studies showed that infections with viruses belonging to specific HPV16 sublineages confer different risks of viral persistence and cancer.

Prevalence of parasitic infections in migrants: do official symptom-driven guidelines apply to the current situation?

In recent years, migration has become a significant challenge in Western countries. Migrant populations, coming from hyper-endemic areas, may present parasitic infections that remain latent and asymptomatic even for years, eventually leading to severe complications. Italian guidelines have been established to perform screening guided by the presence of symptoms and/or hypereosinophilia.

Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients.

Background: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF).

Methods: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month.

Serum IgG2 levels are specifically associated with whole-body insulin-mediated glucose disposal in non-diabetic offspring of type 2 diabetic individuals: a cross-sectional study.

Preclinical studies suggested that IgG2c isotype may specifically impair skeletal muscle insulin sensitivity in mice. In this study we investigated the association between serum levels of the four IgG subclasses and insulin sensitivity in non-diabetic individuals. Total IgG, IgG1, IgG2, IgG3 and IgG4 levels were measured in 262 subjects.

Novel Potent Capsid Assembly Modulators Regulate Multiple Steps of the Hepatitis B Virus Life Cycle.

The assembly of hepatitis B virus (HBV) core protein (HBc) into capsids represents a critical step of viral replication. HBc has multiple functions during the HBV life cycle, which makes it an attractive target for antiviral therapies. Capsid assembly modulators (CAMs) induce the formation of empty capsid or aberrant capsid devoid of pregenomic RNA (pgRNA) and finally block relaxed circular DNA neosynthesis and virion progeny.

Utility of Molecular Identification and Quantitation of Species with Species-Specific Real-Time PCR for Monitoring Treatment Response: A Case Series.

Background: Bartonella species are intracellular bacteria capable of producing several diseases in humans. The three most common and wellknown diseases are cat scratch disease (CSD), caused by B. henselae, trench fever, caused by and Carrion's Disease, caused by .

Depression of lymphocyte activity during cutaneous leishmaniasis: a case report.

Skin leishmaniasis includes lesions of different appearance, shape, and severity, spanning from alarming diffuse lesions to an asymptomatic course. Moreover, aspecific presentation, as well as challenging differential diagnosis of cutaneous leishmaniasis, may request more in-depth investigations on the intriguing and complex pathogenesis of such infection. A 7-year case of worsening cutaneous leishmaniasis in the left frontoparietal region of the scalp, achieving omolateral eyebrow, in a 68-year-old male patient prompted us to address the immunity profile of peripheral blood lymphocytes.

Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals.

Background/aims: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection.

Methods: A retrospective cohort study evaluated eGFR modification during treatment with DAA.

Real-life 3D therapy failure: Analysis of NS5A 93H RAS plus 108 K polymorphism in complex with ombitasvir by molecular modeling.

We report a real-life 3D therapy failure in a patient treated with ombitasvir (OMV)/paritaprevir/ritonavir and dasabuvir without ribavirin (3D-R). He had therapy failure at week 12 after the end of treatment. We detected resistance-associated substitutions (RASs) plus polymorphisms on NS3, NS5A, and NS5B target regions by population sequencing (15% cut-off) at baseline, at relapse and during follow-up.

Probing the interaction interface of the GADD45β/MKK7 and MKK7/DTP3 complexes by chemical cross-linking mass spectrometry.

GADD45β is selectively and constitutively expressed in Multiple Myeloma cells, and this expression correlates with an unfavourable clinical outcome. GADD45β physically interacts with the JNK kinase, MKK7, inhibiting its activity to enable the survival of cancer cells. DTP3 is a small peptide inhibitor of the GADD45β/MKK7 complex and is able to restore MKK7/JNK activation, thereby promoting selective cell death of GADD45β-overexpressing cancer cells.

Increase of Vascular Endothelial Growth Factor and Decrease of MCP-1 and Some Updated Epidemiology Aspects of Cystic Echinococcosis Human Cases in Calabria Region.

We aim to investigate some of the pathogenetic mediators of the human echinococcosis and to obtain updated epidemiological findings on cases of echinococcosis in Calabria, Southern Italy. Echinococcosis diagnosis was based on imaging, serological investigations, and molecular assay. Indeed, real-time PCR indicated the presence of G2/G3 genotypes of complex.

The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals.

Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis.

Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy.

Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1).

Soluble CD14 Subtype-A New Biomarker in Predicting the Outcome of Critically Ill Septic Patients.

Background: We evaluated the role of presepsin (soluble CD14 subtype, sCD14-ST) in predicting the outcome of critically ill septic patients in parallel with procalcitonin and C-reactive protein.

Methods: This study was an observational, prospective study that enrolled 58 surgical and medical intensive care unit patients with suspected sepsis. All studied subjects were retrospectively stratified into survivors and nonsurvivors based on 28 days survival and according to microbiological results in blood culture positive and negative groups.