Further insights on predictors of environmental tobacco smoke exposure during the pediatric age

Background: The smoking ban in public places has reduced Environmental Tobacco Smoke (ETS) exposure for non-smokers, but despite this, domestic environments still remain places at high risk of exposure, and, today, about 40% of children worldwide are exposed to ETS at home. The aims of the study are to investigate the contribution of several factors on ETS exposure among a group of Italian children and to evaluate the changes in smoking precautions adopted at home when the smoker is the mother, the father, or both parents, respectively. Methods: A cross-sectional study was performed on a sample of 519 Italian schoolchildren. Information was collected via a questionnaire. Results: 41.4% of the participants lived with at least one smoker. Almost half of the children exposed to ETS lived with one or more smokers who do not observe any home smoking ban. Lower maternal or paternal educational levels significantly increase the risk of ETS exposure at home and the “worst case” is represented by both parents who smoke. Conclusions: More effective preventive interventions are needed to protect children from ETS exposure. Some interventions should be specifically dedicated to smokers with a low educational level and to mothers that smoke

Extracellular vesicles. New endogenous shuttles for mirnas in cancer diagnosis and therapy?

Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy

Src family kinases as therapeutic targets in advanced solid tumors. What we have learned so far

Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progression

Regenerative potential of DPSCs and revascularization. direct, paracrine or autocrine effect?

A new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration. Graphical abstract: [Figure not available: see fulltext.

Tau oligomers accumulation sensitizes prostate cancer cells to docetaxel treatment

Purpose: Human tau is a highly dynamic, multifunctional protein expressed in different isoforms and conformers, known to modulate microtubule turnover. Tau oligomers are considered pathologic forms of the protein able to initiate specific protein accumulation diseases, called tauopathies. In our study, we investigated the potential association between autophagy and tau oligomers accumulation and its role in the response of prostate cancer cells to docetaxel. Methods: We evaluated in vitro the expression of tau oligomers in prostate cancer cell lines, PC3 and DU145, in presence of autophagy inhibitors and investigated the role of tau oligomers accumulation in resistance to docetaxel treatment. Results: Tau protein was basally expressed in prostate cancer lines as several monomeric and oligomeric forms. The pharmacologic inhibition of autophagy induced in cancer cells the accumulation of tau protein, with a prevalent expression of oligomeric forms. Immunofluorescence analysis of untreated cells revealed that tau was visible mainly in dividing cells where it was localized on the mitotic spindle. Inhibition of autophagy determined an evident upregulation of tau signal in dividing cells and the presence of aberrant monoastral mitotic spindles. The accumulation of tau oligomers was associated with DNA DSB and increased cytotoxic effect by docetaxel. Conclusions: Our data indicate that autophagy could exert a promoting role in cancer growth and during chemotherapy facilitating degradation of tau protein and thus blocking the antimitotic effect of accumulated tau oligomers. Thus, therapeutic strategies aimed at stimulating tau oligomers formation, such as autophagy inhibition, could be an effective adjuvant in cancer therapy

Urinary mercury levels and predictors of exposure among a group of Italian children

Urinary mercury (Hg) levels are suitable to assess long-term exposure to both elemental and inorganic Hg. In this study, the urinary Hg levels of 250 children (aged 6–11 years) from three areas with different anthropogenic impacts in the Rieti province, central Italy, were assessed. The Hg concentrations were in the range of 0.04–2.18 µg L−1 with a geometric mean equal to 0.18 µg L−1 [95% confidence interval (CI), 0.17–0.20 µg L−1] or 0.21 µg g−1 creatinine (95% CI, 0.19–0.23 µg g−1 creatinine), and a reference value calculated as 95th percentile of 0.53 µg L−1 (95% CI, 0.44–0.73 µg L−1) or 0.55 µg g−1 creatinine (95% CI, 0.50–0.83 µg g−1 creatinine). In all cases, urinary Hg data were below the HBM-I values (7 µg L−1 or 5 µg g−1 creatinine) established for urine, while the 95th percentile was above the German Human Biomonitoring Commission’s RV95 (0.4 µg L−1) set for children without amalgam fillings. A significant correlation (p < 0.05) was found between creatinine-corrected results and residence area, with higher urinary Hg levels in children living in the industrial area. Multiple linear regression analysis showed that creatinine was the main predictor of urinary Hg

Targeting lipid rafts as a strategy against coronavirus

Lipid rafts are functional membrane microdomains containing sphingolipids, including gangliosides, and cholesterol. These regions are characterized by highly ordered and tightly packed lipid molecules. Several studies revealed that lipid rafts are involved in life cycle of different viruses, including coronaviruses. Among these recently emerged the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The main receptor for SARS-CoV-2 is represented by the angiotensin-converting enzyme-2 (ACE-2), although it also binds to sialic acids linked to host cell surface gangliosides. A new type of ganglioside-binding domain within the N-terminal portion of the SARS-CoV-2 spike protein was identified. Lipid rafts provide a suitable platform able to concentrate ACE-2 receptor on host cell membranes where they may interact with the spike protein on viral envelope. This review is focused on selective targeting lipid rafts components as a strategy against coronavirus. Indeed, cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, consequently impairing coronavirus adhesion and binding. Moreover, these compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Furthermore, cyclodextrins can assemble into complexes with various drugs to form host–guest inclusions and may be used as pharmaceutical excipients of antiviral compounds, such as lopinavir and remdesivir, by improving bioavailability and solubility. In conclusion, the role of lipid rafts-affecting drugs in the process of coronavirus entry into the host cells prompts to introduce a new potential task in the pharmacological approach against coronavirus