Heparins and 2019-nCoV infection: a narrative review

Abstract. – OBJECTIVE: Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARSCoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis. MATERIALS AND METHODS: We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE. RESULTS: Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-midsized vessels, and it is associated with diffuse alveolar damage. CONCLUSIONS: Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking

Breast milk stem cells: four questions looking for an answer

The finding of stem/progenitor cells in the maternal milk and the discovery of their multilineage potential, associated with some evidence regarding the ability of maternal cells to cross the gastrointestinal barrier and integrate into the organs of the breastfed neonate, has opened an intriguing debate, regarding the strict relationship between mother and son in the postnatal period. In particular, thanks to the discovery of the presence in high quantities of mammary stem cells, a new vision of maternal milk is emerging, in which breastfeeding appears as an unique occasion for reinforcing the physiological development of the newborn, putting all the formulas at a different level of relevance for the neonate. In this contribution the authors try to give an answer to the following 4 questions: 1. is there heterogeneity and a hierarchy among breast milk stem cells? 2. can stem cells present in breast milk enter into the newborn organism? 3. can breast milk stem cells integrate in the neonatal organs and differentiate toward different tissues, including neurons and neuroglia? 4. could metabolomics be useful for the study of stem cells in the human milk

CD44 immunoreactivity in the developing human kidney: a marker of renal progenitor stem cells?

CD44 is a transmembrane adhesion glycoprotein, functioning as a hyaluronan receptor and participating in the uptake and degradation of hyaluronan. Recently, CD44 has been proposed in the adult kidney as a marker of activated glomerular parietal epithelial cells, the putative niche stem cells that, in case of damage to podocytes, might migrate inside the glomerular tuft and undergo transition to podocytes. Here, immunoreactivity for CD44 was tested in 18 human fetuses and newborns with a gestational age ranging from 11 to 39 weeks. CD44 immunoreactivity was observed in all but one developing kidneys, being localized in several renal cell types including intraglomerular, capsular, cortical and medullary interstitial cells and nerve cells. In some cases, CD44 marked scattered cells in nephrogenic subcapsular zone. Our data indicate that CD44 is involved in human nephrogenesis, probably marking a subset of progenitor/stem cells involved in early phases of kidney development and, putatively, in podocyte and/or interstitial cell differentiation

HLA-G expression and role in advanced-stage classical Hodgkin lymphoma

Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-

Genetic Distance from Wolves Affects Family Dogs’ Reactions Towards Howls

Domestication dramatically changes behaviour, including communication, as seen in the case of dogs (Canis familiaris) and wolves (Canis lupus). We tested the hypothesis that domestication may affect an ancient, shared communication form of canids, the howling which seems to have higher individual variation in dogs: the perception and usage of howls may be affected by the genetic relatedness of the breeds to their last common ancestor with wolves (‘root distance’) and by other individual features like age, sex, and reproductive status. We exposed 68 purebred dogs to wolf howl playbacks and recorded their responses. We identified an interaction between root distance and age on the dogs’ vocal and behavioural responses: older dogs from more ancient breeds responded longer with howls and showed more stress behaviours. Our results suggest that domestication impacts vocal behaviour significantly: disintegrating howling, a central, species-specific communication form of canids and gradually eradicating it from dogs’ repertoire

Different Thymosin Beta 4 Immunoreactivity in Foetal and Adult Gastrointestinal Tract

Background: Thymosin beta 4 (T beta(4)) is a member of beta-thymosins, a family of peptides that play essential roles in many cellular functions. A recent study from our group suggested a role for T beta(4) in the development of human salivary glands. The aim of this study was to analyze the expression of T beta(4) in the human gut during development, and in the adult. Methodology/Principal Findings: Immunolocalization of T beta(4) was studied in autoptic samples of tongue, oesophagus, stomach, ileum, colon, liver and pancreas obtained from two human foetuses and two adults. T beta(4) appeared unevenly distributed, with marked differences between foetuses and adults. In the stomach, superficial epithelium was positive in foetuses and negative in adults. Ileal enterocytes were strongly positive in the adult and weakly positive in the foetuses. An increase in reactivity for T beta(4) was observed in superficial colon epithelium of adults as compared with the foetuses. Striking differences were found between foetal and adult liver: the former showed a very low reactivity for T beta(4) while in the adult we observed a strong reactivity in the vast majority of the hepatocytes. A peculiar pattern was found in the pancreas, with the strongest reactivity observed in foetal and adult islet cells. Significance: Our data show a strong expression of T beta(4) in the human gut and in endocrine pancreas during development. The observed differential expression of T beta(4) suggests specific roles of the peptide in the gut of foetuses and adults. The observed heterogeneity of T beta(4) expression in the foetal life, ranging from a very rare detection in liver cells up to a diffuse reactivity in endocrine pancreas, should be taken into account when the role of T beta(4) in the development of human embryo is assessed. Future studies are needed to shed light on the link between T beta(4) and organogenesis