Stard3: A prospective target for cancer therapy

Cancer is one of the major causes of death in developed countries and current therapies are based on surgery, chemotherapeutic agents, and radiation. To overcome side effects induced by chemo-and radiotherapy, in recent decades, targeted therapies have been proposed in second and even first lines. Targeted drugs act on the essential pathways involved in tumor induction, progression, and metastasis, basically all the hallmark of cancers. Among emerging pathways, the cholesterol metabolic pathway is a strong candidate for this purpose. Cancer cells have an accelerated metabolic rate and require a continuous supply of cholesterol for cell division and membrane renewal. Steroidogenic acute regulatory related lipid transfer (START) proteins are a family of proteins involved in the transfer of lipids and some of them are important in non-vesicular cholesterol transportation within the cell. The alteration of their expression levels is implicated in several diseases, including cancers. In this review, we report the latest discoveries on StAR-related lipid transfer protein domain 3 (STARD3), a member of the START family, which has a potential role in cancer, focusing on the structural and biochemical characteristics and mechanisms that regulate its activity. The role of the STARD3 protein as a molecular target for the development of cancer therapies is also discussed. As STARD3 is a key protein in the cholesterol movement in cancer cells, it is of interest to identify inhibitors able to block its activity

Outbreak of sars-cov-2 lineage 20i/501y.V1 in a nursing home underlines the crucial role of vaccination in both residents and staff

Elderly residents in nursing homes are at very high risk of life-threatening COVID-19-related outcomes. In this report, an epidemiological and serological investigation of a SARS-CoV-2 outbreak in an Italian nursing home is described. Among the residents, all but one (19/20) were regularly vaccinated against SARS-CoV-2. In mid-February 2021, a non-vaccinated staff member of the nursing home was diagnosed with the SARS-CoV-2 infection. Following the outbreak investigation, a total of 70% (14/20) of residents aged 77–100 years were found positive. The phylogenetic analysis showed that the outbreak was caused by the SARS-CoV-2 variant of concern 202012/01 (the so-called “UK variant”). However, all but one positive subjects (13/14) were fully asymptomatic. The only symptomatic patient was a vaccinated 86-year-old female with a highly compromised health background and deceased approximately two weeks later. The subsequent serological investigation showed that the deceased patient was the only vaccinated subject that did not develop the anti-spike protein antibody response, therefore being likely a vaccine non-responder. Although the available mRNA SARS-CoV-2 vaccine was not able to prevent several asymptomatic infections, it was able to avert most symptomatic disease cases caused by the SARS-CoV-2 variant of concern 202012/01 in nursing home residents

Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators

Background & Aims: Activation of Kupffer cells and recruitment of monocytes are key events in fibrogenesis. These cells release soluble mediators which induce the activation of hepatic stellate cells (HSCs), the main fibrogenic cell type within the liver. Mer tyrosine kinase (MerTK) signaling regulates multiple processes in macrophages and has been implicated in the pathogenesis of non-alcoholic steatohepatitis-related fibrosis. In this study, we explored if MerTK activation in macrophages influences the profibrogenic phenotype of HSCs. Methods: Macrophages were derived from THP-1 cells or differentiated from peripheral blood monocytes towards MerTK+/CD206+/CD163+/CD209- macrophages. The role of MerTK was assessed by pharmacologic and genetic inhibition. HSC migration was determined in Boyden chambers, viability was measured by the MTT assay, and proliferation was evaluated by the BrdU incorporation assay. Results: Gas-6 induced MerTK phosphorylation and Akt activation in macrophages, and these effects were inhibited by UNC569. During polarization, MerTK+/CD206+/CD163+/CD209- macrophages exhibited activation of STAT3, ERK1/2, p38 and increased expression of VEGF-A. Activation of MerTK in THP-1 macrophages induced a secretome which promoted a significant increase in migration, proliferation, viability and expression of profibrogenic factors in HSCs. Similarly, conditioned medium from MerTK+ macrophages induced a significant increase in cell migration, proliferation, STAT3 and p38 phosphorylation and upregulation of IL-8 expression in HSCs. Moreover, conditioned medium from Gas-6-stimulated Kupffer cells induced a significant increase in HSC proliferation. These effects were specifically related to MerTK expression and activity in macrophages, as indicated by pharmacologic inhibition and knockdown experiments. Conclusions: MerTK activation in macrophages modifies the secretome to promote profibrogenic features in HSCs, implicating this receptor in the pathogenesis of hepatic fibrosis. Lay summary: Fibrosis represents the process of scarring occurring in patients with chronic liver diseases. This process depends on production of scar tissue components by a specific cell type, named hepatic stellate cells, and is regulated by interaction with other cells. Herein, we show that activation of MerTK, a receptor present in a population of macrophages, causes the production of factors that act on hepatic stellate cells, increasing their ability to produce scar tissue

The anticancer activity of an air-stable Pd(i)-NHC (NHC = N-heterocyclic carbene) dimer

A new dinuclear Pd(i) complex coordinating two bis(NHC) ligands revealed an unsuspected stability despite the unsaturation of the two metal centres. Even more surprisingly, the compound showed high and selective antiproliferative activity against different cancer cell lines and ovarian cancer tumoroids, and the mechanism of action was different from that of cisplatin

The anticancer activity of an air-stable Pd(i)-NHC (NHC = N-heterocyclic carbene) dimer

A new dinuclear Pd(i) complex coordinating two bis(NHC) ligands revealed an unsuspected stability despite the unsaturation of the two metal centres. Even more surprisingly, the compound showed high and selective antiproliferative activity against different cancer cell lines and ovarian cancer tumoroids, and the mechanism of action was different from that of cisplatin

How do MNC R&D laboratory roles affect employee international assignments?

Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

Has VZV epidemiology changed in Italy? Results of a seroprevalence study

The aim of the study was to evaluate if and how varicella prevalence has changed in Italy. In particular a seroprevalence study was performed, comparing it to similar surveys conducted in pre-immunization era. During 2013–2014, sera obtained from blood samples taken for diagnostic purposes or routine investigations were collected in collaboration with at least one laboratory/center for each region, following the approval of the Ethics Committee. Data were stratified by sex and age. All samples were processed in a national reference laboratory by an immunoassay with high sensitivity and specificity. Statutory notifications, national hospital discharge database and mortality data related to VZV infection were analyzed as well. A total of 3707 sera were collected and tested. In the studied period both incidence and hospitalization rates decreased and about 5 deaths per year have been registered. The seroprevalence decreased in the first year of life in subjects passively protected by their mother, followed by an increase in the following age classes. The overall antibody prevalence was 84%. The comparison with surveys conducted with the same methodology in 1996–1997 and 2003–2004 showed significant differences in age groups 1–19 y. The study confirms that in Italy VZV infection typically occurs in children. The impact of varicella on Italian population is changing. The comparison between studies performed in different periods shows a significant increase of seropositivity in age class 1–4 years, expression of vaccine interventions already adopted in some regions

Prevalence of Salmonella enterica and Listeria monocytogenes contamination in foods of animal origin in Italy.

The present survey collected and analyzed the results of routine testing for Salmonella enterica and Listeria monocytogenes on foods of animal origin submitted for official controls in Italy during 2001 to 2002. Salmonella was detected in 2.2% of 71,643 food samples examined, and the isolation rates ranged from 9.9% for raw poultry meat to less than 0.1% for dairy products. Isolation rates were also high in raw pork (4.9%) and processed meats (5.3%), which often involved pork. Low rates were observed in seafood (0.5%) and in ready-to-eat foods, such as grocery products (0.7%) and ice creams (0.1%). Serotyping showed that approximately 50% of the isolates belonged to the serotypes most commonly isolated from humans in Italy, thus confirming that most cases of human salmonellosis have a foodborne origin. Levels of L. monocytogenes were higher than what is accepted by the current regulation in 2.4% of 42,300 food samples. The positivity rates ranged from 10.3% in raw pork to none in eggs and egg products. Contamination rates were higher in other meat products (between 2 and 5%) and fish (6.5%) than in cheeses (1.1%) and other dairy products (0.6%). Routine control activities on the microbial contamination of foods can generate data with statistical and epidemiological value. Such data can be used as a basis for estimating the exposure of consumers to foodborne pathogens, following the trends of contamination over time, and evaluating the effects of control measures on the contamination of food

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

<p>Abstract</p> <p>Background</p> <p>Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry.</p> <p>Methods</p> <p>A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV).</p> <p>Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD.</p> <p>Results</p> <p>The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia.</p> <p>Conclusion</p> <p>The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.</p