Study of uptake mechanisms of halloysite nanotubes in different cell lines

Purpose: Halloysite nanotubes (HNTs) are a natural aluminosilicate clay with a chemical formula of Al2Si2O5(OH)4×nH2O and a hollow tubular structure. Due to their peculiar structure, HNTs can play an important role as a drug carrier system. Currently, the mechanism by which HNTs are internalized into living cells, and what is the transport pathway, is still unclear. Therefore, this study aimed at establishing the in vitro mechanism by which halloysite nanotubes could be internalized, using phagocytic and non-phagocytic cell lines as models. Methods: The HNT/CURBO hybrid system, where a fluorescent probe (CURBO) is confined in the HNT lumen, has been used as a model to study the transport pathway mechanisms of HNTs. The cytocompatibility of HNT/CURBO on cell lines model was investigated by MTS assay. In order to identify the internalization pathway involved in the cellular uptake, we performed various endocytosis-inhibiting studies, and we used fluorescence microscopy to verify the nanomaterial internalization by cells. We evaluated the haemolytic effect of HNT/CURBO placed in contact with human red blood cells (HRBCs), by reading the absorbance value of the supernatant at 570 nm. Results: The HNT/CURBO is highly biocompatible and does not have an appreciable haemolytic effect. The results of the inhibition tests have shown that the internalization process of nanotubes occurs in an energy-dependent manner in both the investigated cell lines, although they have different characteristics. In particular, in non-phagocytic cells, clathrin-dependent and independent endocytosis are involved. In phagocytic cells, in addition to phagocytosis and clathrin-dependent endocytosis, microtubules also participate in the halloysite cellular trafficking. Upon internalization by cells, HNT/CURBO is localized in the cytoplasmic area, particularly in the perinuclear region. Conclusion: Understanding the cellular transport pathways of HNTs can help in the rational design of novel drug delivery systems and can be of great value for their applications in biotechnology

A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases

Antithrombin Plasma Levels and Fibtem Determination in Children with Acute Lymphoblastic Leukemia Undergoing Asparaginase Treatment

none5noneBiddeci G; Sanna G; Geranio G; Spiezia L; et al.Biddeci, G; Sanna, G; Geranio, G; Spiezia, L; Et, Al

Secular trends in growth of African Pygmies and Bantu

OBJECTIVE: The aim of this study was to investigate whether a secular trend in growth occurred during the last century in Pygmies from Cameroon (West Pygmies) and in Bantu rural farmers, the latter being studied to serve as controls.-DESIGN: The evolution in height of West Pygmies and Bantu farmers from 1911 to 2006 was evaluated using data from the literature as well as data gathered by our research team during an expedition to Cameroon in 2006. RESULTS: During the last century, no secular trend in west Pygmies is apparent, as height changed from 151 cm to 155 cm in males and from 143 cm to 146 cm in females. A small though significant (p=0.026), increment (about 2 cm) was observed only in female subjects during the last ten years. By contrast, Bantu heights show a significant change from 1943 to 2006 for both males (from 159 cm to 172 cm; p=0.025) and females (from 148 cm to 160 cm; p=0.029). CONCLUSIONS: Over the last century, the Bantu population exhibited a significant secular trend for height, whereas West Pygmies did not increase their linear growth. The lack of secular trend in Pygmies possibly suggests that their stature reflects adaptation to the forest lifestyle. We may hypothesize that not only environmental but epigenetic factors have also contributed to their growth potential

Halloysite nanotubes loaded with peppermint essential oil as filler for functional biopolymer film

The purpose of this paper is to show how a functional bionanocomposite film with both antioxidant and antimicrobial activities was successfully prepared by the filling of a pectin matrix with modified Halloysite nanotubes (HNT) containing the essential peppermint oil (PO). Firstly, HNT surfaces were functionalized with cucurbit[6]uril (CB[6]) molecules with the aim to enhance the affinity of the nanofiller towards PO, which was estimated by means of HPLC experiments. The HNT/CB[6] hybrid was characterized by several methods (thermogravimetry, FT-IR spectroscopy and scanning electron microscopy) highlighting the influence of the supramolecular interactions on the composition, thermal behavior and morphology of the filler. Then, a pectin + HNT/CB[6] biofilm was prepared by the use of the casting method under specific experimental conditions in order to favor the entrapment of the volatile PO into the nanocomposite structure. Water contact angle measurements, thermogravimetry and tensile tests evidenced the effects of the modified filler on the thermo-mechanical and wettability properties of pectin, which were correlated to the microscopic structure of the biocomposite film. In addition, PO release in food simulant solvent was investigated at different temperatures (4 and 25 \ub0C), whereas the antioxidant activity of the nanocomposite film was estimated using the DPPH method. Finally, we studied the in vitro antibacterial activity of the biofilm against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which were isolated by beef and cow milk, respectively. These experiments were carried out at specific temperatures (4, 37 and 65 \ub0C) that can be useful for a multi-step food conservation. This paper puts forwards an easy strategy to prepare a functional sustainable edible film with thermo-sensitive antioxidant/antimicrobial activity

Mucormycosis with peculiar aortic involvement in a child with acute lymphoblastic leukemia

Among fungal infection, mucormycosis is a rare but severe etiology in immunocompromised patients. Lung and sinus are the usual sites; the involvement of blood vessels is also described. The diagnosis is a real challenge, because blood tests (galactomannan, beta-D-glucan) are negative and the only diagnostic tool is usually the biopsy of the affected zone. Aortitis is rare and usually caused by bacterial infection, fungal etiology is unusual and only episodic cases are reported in literature. Medical therapy alone is usually not sufficient and debilitating surgical intervention is required. We report the case of a child affected by B precursor acute lymphoblastic leukemia, presenting a systemic fungal infection complicated by aortitis, probably due to Mucor. The patient developed fever and pneumonia during the Induction phase of chemotherapy. At the beginning, the infection was treated as bacterial and the diagnosis of Mucor infection was possible only after surgical intervention with histological analysis. Medical therapy (antifungal) was not sufficient alone to cure the infection and an urgent surgical intervention was required. This case underlines the challenge in the diagnosis of mucomycosis, that should be suspected in case of prolonged fever during aplasia, not responding to standard antibiotic and antifungal therapies. Mucor infection often require a combined intervention, both medical and surgical to cure the infection