Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1.

Some hepatitis C virus (HCV) proteins, including core protein, deregulate the cell cycle of infected cells, thereby playing an important role in the viral pathogenesis of HCC. Thus far, there are only few studies that have deeply investigated in depth the effects of the HCV core protein expression on the progression through the G1/S and G2/M phases of the cell cycle. To shed light on the molecular mechanisms by which the HCV core protein modulates cell proliferation, we have examined its effects on cell cycle in hepatocarcinoma cells. We show here that HCV core protein perturbs progression through both the G1/S and the G2/M phases, by modulating the expression and the activity of several cell cycle regulatory proteins. In particular, our data provided evidence that core-dependent deregulation of the G1/S phase and its related cyclin-CDK complexes depends upon the ERK1/2 pathway. On the other hand, the viral protein also increases the activity of the cyclin B1-CDK1 complex via the p38 MAPK and JNK pathways. Moreover, we show that HCV core protein promotes nuclear import of cyclin B1, which is affected by the inhibition of both the p38 and the RNA-dependent protein kinase (PKR) activities. The important role of p38 MAPK in regulating G2/M phase transition has been previously documented. It is becoming clear that PKR has an important role in regulating both the G1/S and the G2/M phase, in which it induces M phase arrest. Based on our model, we now show, for the first time, that HCV core expression leads to deregulation of the mitotic checkpoint via a p38/PKR-dependent pathway

Genomic analysis of Sardinian 26544/OG10 isolate of African swine fever virus

Abstract Comparative genomic analysis aims to underscore genetic assortment diversification in distinct viral isolates, to identify deletions and to carry out evolutionary studies. We sequenced the first complete genome of an ASFV p72 genotype I strain isolated from domestic pigs in Sardinia (Italy) using Next-Generation Sequence (NGS) technology. The genome is 182,906 bp long, contains 164 ORFs and has a 99.20% nucleotide identity to the L60 strain. Comparison analysis against the 16 ASFV genomes available in the database showed that 136 ORFs are present in nine ASFV isolates annotated to date. The most divergent ORFs codify for uncharacterized proteins such as X69R and DP96R, which have 51.3% and 70.4% nucleotide identity to the other isolates. A comparison between the Sardinian isolate and the avirulent isolates OURT 88/3, NHV, BA71V was also carried out. Major variations were found within the multigene families (MGFs) located in the left and right genome regions

Squamous-cell carcinoma of the tongue following therapy of rheumatoid arthritis with abatacept

A patient affected by rheumatoid arthritis developed a squamous-cell carcinoma probably due to abatacept, according to Naranjo algorithm. The case describes this adverse reaction for the first time and highlights the need for additional studies to establish the long-term risk profile of abatacept

Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1

Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two human viruses: the Herpes simplex virus type 1 (HSV-1) and the pandemic and currently widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 40 phenolic compounds were identified in the extract by HPLC-MS/MS analysis: most of them were quercetin derivatives, others included derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin, and scutellarein. Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 μg/mL. These results are very promising and highlight how natural extracts could be used in the design of antiviral drugs and the development of future vaccines

in vitro activity of essential oils against pseudomonas aeruginosa isolated from infected hip implants

Introduction: Essential oils have been used since ancient times and are known for their anti-inflammatory, anti-depressive, antiseptic, antifungal and antimicrobial properties. Methodology: in this study the antimicrobial activity of two essential oils from Melaleuca alternifolia and Thymus vulgaris–red thyme geraniol was tested against 16 multidrug-resistant P. aeruginosa strains from infected hip implants as well as the "in vitro" cytotoxic activity on normal human Wong-Kilbourne derivative (WKD) cells. Results: Thymus vulgaris–red thyme geraniol showed lower antimicrobial activity when compared to Melaleuca alternifolia. All tested oils were cytotoxic at concentrations lower than 0.12%. Conclusion: Increase in drug resistance and lack of new antibiotics may encourage the development of natural treatments together with higher concern on environmental issues and natural lifestyle

Biological activities of essential oil extracted from leaves of Atalantia sessiflora Guillauminin Vietnam

Introduction: The present study aimed to determine the chemical compositions and bioactivities of the essential oil of Atalantia sessifloraGuillaumin (A. sessiflora), including antibacterial, antimycotic, antitrichomonas, anti-inflammatory and antiviral effects. Methodology: The essential oil from leaves of A. sessiflora was extracted by hydrodistillation using a Clevenger apparatus. Chemical compositions of oil were identified by GC/MS. Antimicrobial and antitrichomonas activity were determined by the microdilution method; anti-inflammatory and antiviral were determined by the MTT method. Results: The average yield of oil was 0.46 ± 0.01% (v/w, dry leaves). A number of 45 constituents were identified by GC/MS. The essential oil comprised four main components. The oil showed antimicrobial activities against Gram-positive strains as Staphylococcus; Gram-negative bacteria such as Klebsiella pneumoniae and Escherichia coli; and finally four Candidaspecies. Enterococcus faecalis and Pseudomonas aeruginosawere least susceptible to the oil of A. sessiflora, as seen in their MIC and MLC values over 16% (v/v). Activity against Trichomonas vaginalis was also undertaken, showing IC50, IC90 and MLC values of 0.016, 0.03 and 0.06% (v/v) respectively, after 48 hours of incubation. The oil of A. sessiflora displayed activity against the nitric oxide generation with the IC50 of 95.94 ± 6.18 μg/mL. The oil was completely ineffective against tested viruses, ssRNA+, ssRNA-, dsRNA, and dsDNA viruses. Conclusions: This is the first yet comprehensive scientific report about the chemical compositions and pharmacological properties of the essential oil of A. sessiflora. Further studies should be done to evaluate the safety and toxicity of A. sessiflora oil

Prevalence of peripheral arterial disease in subjects with moderate cardiovascular risk: Italian results from the PANDORA study Data from PANDORA (Prevalence of peripheral Arterial disease in subjects with moderate CVD risk, with No overt vascular Diseases nor Diabetes mellitus)

<p>Abstract</p> <p>Background</p> <p>The PANDORA study has recently examined the prevalence of low ankle brachial index (ABI) in subjects with moderate risk of cardiovascular disease. This sub-analysis of the PANDORA study examines the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by ABI, in Italian subjects presenting with moderate cardiovascular risk, in the absence of diabetes or overt vascular disease.</p> <p>Methods</p> <p>PANDORA is a non-interventional, cross-sectional study that was performed in 6 European countries, involving subjects with at least one cardiovascular (CV) risk factor. The primary objective was to evaluate the prevalence of asymptomatic PAD using ABI. For this post-hoc sub-analysis, data were extracted for subjects enrolled in Italy, comprising 51.5% (n = 5298) of subjects from the original PANDORA study. Secondary objectives were to establish the prevalence and treatment of CV risk factors.</p> <p>Results</p> <p>The mean age was 63.9 years and 22.9% (95% CI 21.7-24.0) of subjects presented with asymptomatic PAD. A range of risk factors comprising smoking, hypertension, low HDL-cholesterol, family history of coronary heart disease and habit of moderate-high alcohol intake were significantly associated with asymptomatic PAD (p < 0.0001). Statin treatment had the lowest incidence in Italian subjects. Furthermore, patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (p = 0.0001).</p> <p>Conclusions</p> <p>Asymptomatic PAD was highly prevalent in Italian subjects, the majority of whom were not candidates for ABI assessment according to current guidelines. Findings from this study suggest that these patients should be carefully examined in clinical practice and ABI measured so that therapeutic interventions known to decrease their CV risk may be offered.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00689377">NCT00689377</a></p

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Results of the providune project: Restoration of the "Coastal dunes with Juniperus spp." priority habitat in Sardinia

The Providune project "Conservation and restoration of habitats dune in the sites of the Provinces of Cagliari, Matera and Caserta" (LIFE07NAT/IT/000519), financed by the European Union for the years 2009-2014, was aimed to protect and restore the "coastal dunes with Juniperus spp." habitat (code 2250â\u88\u97) and other related habitats of community interest characterizing the Mediterranean sandy coasts. In this paper will be shown the main results of the project focusing on the geobotanical studies, ex situ conservation and restoration activities carried out in three Site of Community Importance (SCI) areas selected in the South Sardinia. The geobotanical analyses were carried out in order to characterize the flora and vegetation of the Juniperus habitat and the particular ecological traits of Juniperus macrocarpa respectively. In addition, three detailed maps related to the habitat and vegetation for each coastal dune systems were drawn. To carry out the ex situ conservation of coastal dune plants, germplasm (seeds and fruits) was collected and stored in the Sardinian Germplasm Bank (BG-SAR); moreover effective protocols for the germination of 12 key species of the Juniperus habitat were identified, for the purpose of obtain their propagation and reinforcement. An experimental project to reinforce the native germplasm of structural species of coastal habitats such as Pancratium maritimum, Pistacia lentiscus and J. macrocarpa was realized, using the grafting groups that is sand trap systems that encouraged the embryonic dunes formation and dune consolidation, and permanent plots (bio-mats coconut fiber installed to reduce wind erosion and protect the plant roots) previously installed, with the aim to reinforce species populations and contain habitat fragmentation. Restoration actions were performed ensuring the manual removal of invasive alien plant species and the subsequent planting of native ones. Other measures to reduce the human impacts, mainly due to trampling, such as wooden walkways and light fences were realized. Finally, once completed all conservation actions and interventions, the monitoring protocol to verify their effectiveness has been activated; this action will be implemented in the next five years, based on the post-Life monitoring plan