Design, synthesis and biological evaluation of new H2S-releasing rivastigmine derivatives as neuroprotective molecules.

Alzheimer's disease (AD) represents one of the main challenges for the 21st century medical research as no disease-modifying agent has been successfully progressed to the market, while the number of people affected by AD is estimated to grow exponentially over the next years. The complex network of triggering factors involved in the insurgence and progression of AD can be rightly addressed as one of the main reasons behind the difficulty in identifying new pharmacological approaches. For this reason, the discovery and development of drugs endowed with pleiotropic activity remain the most valuable, but at the same time challenging, approaches to tackle down AD.

Melanocortin receptor 4 as a new target in melanoma therapy: Anticancer activity of the inhibitor ML00253764 alone and in association with B-raf inhibitor vemurafenib.

The aim of our study is to investigate in vitro and in vivo MC4R as a novel target in melanoma using the selective antagonist ML00253764 (ML) alone and in combination with vemurafenib, a B-rafV600E inhibitor. The human melanoma B-raf mutated A-2058 and WM 266-4 cell lines were used. An MC4R null A-2058 cell line was generated using a CRISPR/Cas9 system.

Inhibiting immunoregulatory amidase NAAA blocks ZIKV maturation in Human Neural Stem Cells.

Recent evidence suggests that lipids play a crucial role in viral infections beyond their traditional functions of supplying envelope and energy, and creating protected niches for viral replication. In the case of Zika virus (ZIKV), it alters host lipids by enhancing lipogenesis and suppressing β-oxidation to generate viral factories at the endoplasmic reticulum (ER) interface. This discovery prompted us to hypothesize that interference with lipogenesis could serve as a dual antiviral and anti-inflammatory strategy to combat the replication of positive sense single-stranded RNA (ssRNA+) viruses.

Lipid balance remodelling by human positive-strand RNA viruses and the contribution of lysosomes.

A marked reorganization of internal membranes occurs in the cytoplasm of cells infected by single stranded positive-sense RNA viruses. Most cell compartments change their asset to provide lipids for membrane rearrangement into replication organelles, where to concentrate viral proteins and enzymes while hiding from pathogen pattern recognition molecules. Because the endoplasmic reticulum is a central hub for lipid metabolism, when viruses hijack the organelle to form their replication organelles, a cascade of events change the intracellular environment.

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels.

Background: Experimental evidence suggests a key role of SIRT1 (silent information regulator 1) in age- and metabolic-related vascular dysfunction. Whether these effects hold true in the human microvasculature is unknown. We aimed to investigate the SIRT1 role in very early stages of age- and obesity-related microvascular dysfunction in humans.

Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor.

Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble.

A low-cost simple test for weekly detection of Mycoplasma hyorhinis and arginini contaminations in cell cultures and viral preparations.

Mollicutes (Mycoplasma and Acholeplasma) are parasitic bacteria that adhere to cellular surfaces, naturally resistant to many antibiotics and extremely small. They are often found as contaminants in cultured cells, where they go unnoticed. They may be present in viral stocks because they are present in supernatants of cells where cultured viruses are released.

Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin.

Acid ceramidase (AC) is a lysosomal hydrolase encoded by the ASAH1 gene, which cleaves ceramides into sphingosine and fatty acid. AC is expressed at high levels in most human melanoma cell lines and may confer resistance against chemotherapeutic agents. One such agent, doxorubicin, was shown to increase ceramide levels in melanoma cells.

Ablation of Acid Ceramidase Impairs Autophagy and Mitochondria Activity in Melanoma Cells.

Cutaneous melanoma is often resistant to therapy due to its high plasticity, as well as its ability to metabolise chemotherapeutic drugs. Sphingolipid signalling plays a pivotal role in its progression and metastasis. One of the ways melanoma alters sphingolipid rheostat is via over-expression of lysosomal acid ceramidase (AC), which catalyses the hydrolysis of pro-apoptotic long-chain ceramides into sphingosine and fatty acid.

Sphingolipid/Ceramide Pathways and Autophagy in the Onset and Progression of Melanoma: Novel Therapeutic Targets and Opportunities.

Melanoma is a malignant tumor deriving from neoplastic transformation of melanocytes. The incidence of melanoma has increased dramatically over the last 50 years. It accounts for most cases of skin cancer deaths.

Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts.

Background: Enhancement of the osteogenic potential of mesenchymal stem cells (MSCs) is highly desirable in the field of bone regeneration. This paper proposes a new approach for the improvement of osteogenesis combining hypergravity with osteoinductive nanoparticles (NPs).

Materials And Methods: In this study, we aimed to investigate the combined effects of hypergravity and barium titanate NPs (BTNPs) on the osteogenic differentiation of rat MSCs, and the hypergravity effects on NP internalization.