RICTOR/mTORC2 downregulation in BRAF melanoma cells promotes resistance to BRAF/MEK inhibition.

Background: The main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF-mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to assess in this context the role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit, regarded as an oncogenic driver in several tumor types, including MM.

Methods: After analyzing The Cancer Genome Atlas MM patients' database to explore both overall survival and molecular signatures as a function of intra-tumor RICTOR levels, we investigated the effects of RICTOR downregulation in BRAF MM cell lines on their response to BRAF/MEKi.

Long-Term Outcomes Stratified by Age in Patients with a Mechanical versus Biological Mitral Valve Replacement.

Objectives: Balancing anticoagulation and reoperation risks determines prostheses choice (mechanical/biological) for mitral valve replacement. We aimed to re-evaluate the outcomes after biological versus mechanical mitral valve replacement. Methods: We compared long-term benefits and risks of mechanical and biological prostheses in 2056 patients (52% men, 48% women; 65.

Effect of Temperature and pH on the Secondary Structure and Denaturation Process of Jumbo Squid Hepatopancreas Cathepsin D.

Background: Cathepsin D is a lysosomal enzyme that is found in all organisms acting in protein turnover, in humans it is present in some types of carcinomas, and it has a high activity in Parkinson's disease and a low activity in Alzheimer disease. In marine organisms, most of the research has been limited to corroborate the presence of this enzyme. It is known that cathepsin D of some marine organisms has a low thermostability and that it has the ability to have activity at very acidic pH.

Patterns of clinical nail appearances in patients with cutaneous psoriasis.

Background And Aim: Nail manifestations are often an overlooked aspect in psoriatic disease, cutaneous and joint involvement being far more often reported and investigated. The reported prevalence of nail changes varies in literature, specific fingernail clinical features having different degrees of occurrence. The aim of this study was to describe specific clinical patterns of fingernail alterations in adult patients with plaque-type psoriasis in a university hospital in the North-West of Romania.

Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy.

Background/aims: Human milk is considered the most suitable food for infants. The potential benefits of breastfeeding can be explained by the presence of different growth and neurotrophic factors in human milk. This study was designed to detect some biomarkers in human milk, which could be involved in the infant neurodevelopment and in the regulation of the maturation of neonatal intestine (brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21), lysophosphatidic acid (LPA) and autotaxin (ATX)), and compare them on the basis of the consumption of iodine supplements or multivitamins.