Overexpression of mir-489-3p inhibits proliferation and migration of non-small cell lung cancer cells by suppressing the HER2/PI3K/AKT/Snail signaling pathway.

Background: Lung cancer is a highly prevalent malignancy with significant morbidity and mortality rates. MiR-489-3p, a microRNA, has been identified as a regulator of tumor cell proliferation and invasion. Its expression is downregulated in non-small cell lung cancer (NSCLC).

Searching for Suitable Kojic Acid Coformers: From Cocrystals and Salt to Eutectics.

The possibility of obtaining cocrystals of kojic acid with organic coformers has been investigated by both computational and experimental approaches. Cocrystallization attempts have been carried out with about 50 coformers, in different stoichiometric ratios, by solution, slurry, and mechanochemical methods. Cocrystals were obtained with 3-hydroxybenzoic acid, imidazole, 4-pyridone, DABCO, and urotropine, while piperazine yielded a salt with the kojiate anion; cocrystallization with theophylline and 4-aminopyridine resulted in stoichiometric crystalline complexes that could not be described with certainty as cocrystals or salts.

Exploring the Co-Crystallization of Kojic Acid with Silver(I), Copper(II), Zinc(II), and Gallium(III) for Potential Antibacterial Applications.

Co-crystallization of kojic acid (HKA) with silver(I), copper(II), zinc(II), or gallium(III) salts yielded three 1D coordination polymers and one 0D complex in which kojic acid was present as a neutral or anionic terminal or bridging ligand. All reactions were conducted mechanochemically via ball milling and manual grinding, or via slurry. All solids were fully characterized via single-crystal and/or powder X-ray diffraction.

Humanized mice for investigating SARS-CoV-2 lung infection and associated human immune responses.

There is an urgent need for animal models of coronavirus disease 2019 to study immunopathogenesis and test therapeutic intervenes. In this study, we showed that NOD/SCID IL2rg (NSG) mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-Sequencing identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, IFN stimulation and pulmonary fibrosis, between HL grafts from infected and control NSG-L mice.

Proteomic and Metabolomic Characterization of SARS-CoV-2-Infected Cynomolgus Macaque at Early Stage.

Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs.

Steps towards a nature inspired inorganic crystal engineering.

This Perspective outlines the results obtained at the University of Bologna by applying crystal engineering strategies to develop nature inspired organic-inorganic materials to tackle challenges in the health and environment sectors. It is shown by means of a number of examples that co-crystallization of inorganic salts, such as alkali and transition metal halides, with organic compounds, such as amino acids, urea, thiourea and quaternary ammonium salts, can be successfully used for (i) chiral resolution and conglomerate formation from racemic compounds, (ii) inhibition of soil enzyme activity in order to reduce urea decomposition and environmental pollution, and (iii) preparation of novel agents to tackle antimicrobial resistance. All materials described in this Perspective have been obtained by mechanochemical solvent-free or slurry methods and characterized by solid state techniques.

Generation of immunodeficient pig with hereditary tyrosinemia type 1 and their preliminary application for humanized liver.

Background: Mice with humanized livers are important models to study drug toxicology testing, development of hepatitis virus treatments, and hepatocyte transplantation therapy. However, the huge difference between mouse and human in size and anatomy limited the application of humanized mice in investigating human diseases. Therefore, it is urgent to construct humanized livers in pigs to precisely investigate hepatocyte regeneration and human hepatocyte therapy.

Incompatibility between recipient CD47 and donor SIRPα is not a key risk factor for thrombocytopenia or anemia following rat liver xenotransplantation in mice.

Liver xenotransplantation (LXT) is greatly impeded by severe thrombocytopenia, anemia, and coagulopathy. Hepatic phagocytic cells are thought to play an important role in LXT-induced thrombocytopenia and anemia. In this study, we investigated whether the lack of recipient CD47-donor SIRPα interaction, which is known to induce xenograft rejection by macrophages, exacerbates platelet and RBC depletion following LXT.

IL2RG-deficient minipigs generated via CRISPR/Cas9 technology support the growth of human melanoma-derived tumours.

Objectives: Immunodeficient mice injected with human cancer cell lines have been used for human oncology studies and anti-cancer drug trials for several decades. However, rodents are not ideal species for modelling human cancer because rodents are physiologically dissimilar to humans. Therefore, anti-tumour drugs tested effective in rodents have a failure rate of 90% or higher in phase III clinical trials.

Different effects of lysophosphatidic acid on L-type calcium current in neonatal rat ventricular myocytes with and without H2O2 treatment.

L-type calcium current (I(Ca-L)) alterations are implicated in various cardiac diseases, and the lysophosphatidic acid (LPA) level increases in several ischemic heart diseases. We investigated the effects of LPA on I(Ca-L) in normal and H2O2-treated neonatal rat ventricular myocytes. LPA treatment (24h) increased the action potential duration (APD) and I(Ca-L) in normal ventricular myocytes, but it decreased these parameters in H2O2-treated myocytes.