The potential of TRP channels as new prognostic and therapeutic targets against prostate cancer progression.

Prostate cancer (PCa) is the second deadliest cancer among men worldwide. Particularly critical is its development towards metastatic androgen-independent forms for which the current therapies are ineffective. Indeed, the 5-year relative survival for PCa drops dramatically to 34 % in the presence of metastases.

Osteoblast Response to Widely Ranged Texturing Conditions Obtained through High Power Laser Beams on Ti Surfaces.

Titanium and titanium alloys are the prevailing dental implant materials owing to their favorable mechanical properties and biocompatibility, but how roughness dictates the biological response is still a matter of debate. In this study, laser texturing was used to generate eight paradigmatic roughened surfaces, with the aim of studying the early biological response elicited on MC3T3-E1 pre-osteoblasts. Prior to cell tests, the samples underwent SEM analysis, optical profilometry, protein adsorption assay, and optical contact angle measurement with water and diiodomethane to determine surface free energy.

Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.

Congenital hydrocephalus (CH), occurring in approximately 1/1,000 live births, represents an important clinical challenge due to the limited knowledge of underlying molecular mechanisms. The discovery of novel CH genes is thus essential to shed light on the intricate processes responsible for ventricular dilatation in CH. Here, we identify FLVCR1 (feline leukemia virus subgroup C receptor 1) as a gene responsible for a severe form of CH in humans and mice.

Modulation of purinergic signaling in endothelial cells by tumor microenvironment.

Purinergic signaling plays a crucial role in vascular endothelium functions. In particular, ionotropic P2X receptors (P2XRs) are engaged in various intracellular pathways through which endothelial cells (ECs) adapt to external stimuli. However, very little is known about the impact of P2XRs on vascular remodeling during carcinogenesis.

The Emerging Concept of Transportome: State of the Art.

The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters. For all these reasons, physiologists have long been interested in the expression and functionality of ion channels and transporters, in both physiological and pathological settings and across the different domains of life.

The fallacy of functional nomenclature in the kingdom of biological multifunctionality: physiological and evolutionary considerations on ion channels.

Living organisms are multiscale complex systems that have evolved high degrees of multifunctionality and redundancy in the structure-function relationship. A number of factors, only in part determined genetically, affect the jobs of proteins. The overall structural organization confers unique molecular properties that provide the potential to perform a pattern of activities, some of which are co-opted by specific environments.

Mechanical and Biological Characterization of PMMA/AlO Composites for Dental Implant Abutments.

The mechanical and biological behaviors of PMMA/AlO composites incorporating 30 wt.%, 40 wt.%, and 50 wt.

The US21 viroporin of human cytomegalovirus stimulates cell migration and adhesion.

The human cytomegalovirus (HCMV) US12 gene family contributes to virus-host interactions by regulating the virus' cell tropism and its evasion of host innate immune responses. US21, one of the 10 US12 genes (US12-US21), is a descendant of a captured cellular transmembrane BAX inhibitor motif-containing gene. It encodes a 7TMD endoplasmic reticulum (ER)-resident viroporin (pUS21) capable of reducing the Ca content of ER stores, which, in turn, protects cells against apoptosis.

The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis.

The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical-physical features of the matrix, while others may come from the 'outer' environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted.

Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis.

The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a transmembrane heme exporter essential for embryonic vascular development. However, the exact role of FLVCR1a during blood vessel development remains largely undefined. Here, we show that FLVCR1a is highly expressed in angiogenic endothelial cells (ECs) compared to quiescent ECs.

Bacterial and Cellular Response to Yellow-Shaded Surface Modifications for Dental Implant Abutments.

Dental implants have dramatically changed the rehabilitation procedures in dental prostheses but are hindered by the possible onset of peri-implantitis. This paper aims to assess whether an anodization process applied to clinically used surfaces could enhance the adhesion of fibroblasts and reduce bacterial adhesion using as a reference the untreated machined surface. To this purpose, four different surfaces were prepared: (i) machined (MAC), (ii) machined and anodized (Y-MAC), (iii) anodized after sand-blasting and acid etching treatment (Y-SL), and (iv) anodized after double acid etching (Y-DM).

BioTEA: Containerized Methods of Analysis for Microarray-Based Transcriptomics Data.

Tens of thousands of gene expression data sets describing a variety of model organisms in many different pathophysiological conditions are currently stored in publicly available databases such as the Gene Expression Omnibus (GEO) and ArrayExpress (AE). As microarray technology is giving way to RNA-seq, it becomes strategic to develop high-level tools of analysis to preserve access to this huge amount of information through the most sophisticated methods of data preparation and processing developed over the years, while ensuring, at the same time, the reproducibility of the results. To meet this need, here we present bioTEA (biological Transcript Expression Analyzer), a novel software tool that combines ease of use with the versatility and power of an R/Bioconductor-based differential expression analysis, starting from raw data retrieval and preparation to gene annotation.

The Transcriptional Landscape of Wild Type Metastatic Melanoma: A Pilot Study.

Melanoma is a relatively rare disease worldwide; nevertheless, it has a great relevance in some countries, such as in Europe. In order to shed some light upon the transcriptional profile of skin melanoma, we compared the gene expression of six independent tumours (all progressed towards metastatic disease and with wild type ) to the expression profile of non-dysplastic melanocytes (considered as a healthy control) in a pilot study. Paraffin-embedded samples were manually micro-dissected to obtain enriched samples, and then, RNA was extracted and analysed through a microarray-based approach.

P2X Purinergic Receptors Are Multisensory Detectors for Micro-Environmental Stimuli That Control Migration of Tumoral Endothelium.

The tumoral microenvironment often displays peculiar features, including accumulation of extracellular ATP, hypoxia, low pH-acidosis, as well as an imbalance in zinc (Zn) and calcium (Ca). We previously reported the ability of some purinergic agonists to exert an anti-migratory activity on tumor-derived human endothelial cells (TEC) only when applied at a high concentration. They also trigger calcium signals associated with release from intracellular stores and calcium entry from the external medium.

Endothelial Cells Promote Osteogenesis by Establishing a Functional and Metabolic Coupling With Human Mesenchymal Stem Cells.

Bone formation involves a complex crosstalk between endothelial cells (EC) and osteodifferentiating stem cells. This functional interplay is greatly mediated by the paracrine and autocrine action of soluble factors released at the vasculature-bone interface. This study elucidates the molecular and functional responses triggered by this intimate interaction.

Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment.

The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth.

Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry.

The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc.

Proanthocyanidins and Where to Find Them: A Meta-Analytic Approach to Investigate Their Chemistry, Biosynthesis, Distribution, and Effect on Human Health.

Proanthocyanidins (PACs) are a class of polyphenolic compounds that are attracting considerable interest in the nutraceutical field due to their potential health benefits. However, knowledge about the chemistry, biosynthesis, and distribution of PACs is limited. This review summarizes the main chemical characteristics and biosynthetic pathways and the main analytical methods aimed at their identification and quantification in raw plant matrices.

A Transcriptomic Approach Reveals Selective Ribosomal Remodelling in the Tumour Versus the Stromal Compartment of Metastatic Colorectal Cancer.

Because of its high incidence and poor prognosis, colorectal cancer (CRC) represents an important health issue in several countries. As with other carcinomas, the so-called tumour microenvironment (TME) has been shown to play key roles in CRC progression and related therapeutical outcomes, even though a deeper understanding of the underlying molecular mechanisms is needed to devise new treatment strategies. For some years now, omics technologies and consolidated bioinformatics pipelines have allowed scientists to access large amounts of biologically relevant information, even when starting from small tissue samples; thus, in order to shed new light upon the role of the TME in CRC, we compared the gene expression profiles of 6 independent tumour tissues (all progressed towards metastatic disease) to the expression profile of the surrounding stromata.

Bioactive Triterpenes of Gum Resin Extract Display Cholesterol-Lowering Potential.

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects.

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development.

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients.

Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.

Calcium (Ca)-permeable channels are key players in different processes leading to blood vessel formation via sprouting angiogenesis, including endothelial cell (EC) proliferation and migration, as well as in controlling vascular features which are typical of the tumor vasculature.In this review we present an up-to-date and critical view on the role of Ca-permeable channels in tumor vascularization, emphasizing on the dual communication between growth factors (mainly VEGF) and Ca signals. Due to the complexity of the tumor microenvironment (TME) as a source of multiple stimuli acting on the endothelium, we aim to discuss the close interaction between chemical and physical challenges (hypoxia, oxidative stress, mechanical stress) and endothelial Ca-permeable channels, focusing on transient receptor potential (TRP), store-operated Ca channels (SOCs), and mechanosensitive Piezo channels.

MORPHEUS: An automated tool for unbiased and reproducible cell morphometry.

Here we present a new Fiji/ImageJ2 plugin called Multiparametric Morphometric Analysis of EUcaryotic cellS (MORPHEUS), designed for the automated evaluation of cell morphometry from images acquired by fluorescence microscopy. MORPHEUS works with sampling distributions to learn-in an unsupervised manner and by a nonparametric approach-how to recognize the cells suitable for subsequent analysis. Afterward, the algorithm performs the evaluation of the most relevant cell-shape descriptors over the full set of detected cells.