Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.     

From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish

Organoids are tiny, self-organized, three-dimensional tissue cultures that are derived from the differentiation of stem cells. The growing interest in the use of organoids arises from their ability to mimic the biology and physiology of specific tissue structures in vitro. Organoids indeed represent promising systems for the in vitro modeling of tissue morphogenesis and organogenesis, regenerative medicine and tissue engineering, drug therapy testing, toxicology screening, and disease modeling. Although 2D cell cultures have been used for more than 50 years, even for their simplicity and low-cost maintenance, recent years have witnessed a steep rise in the availability of organoid model systems. Exploiting the ability of cells to re-aggregate and reconstruct the original architecture of an organ makes it possible to overcome many limitations of 2D cell culture systems. In vitro replication of the cellular micro-environment of a specific tissue leads to reproducing the molecular, biochemical, and biomechanical mechanisms that directly influence cell behavior and fate within that specific tissue. Lineage-specific self-organizing organoids have now been generated for many organs. Currently, growing cardiac organoid (cardioids) from pluripotent stem cells and cardiac stem/progenitor cells remains an open challenge due to the complexity of the spreading, differentiation, and migration of cardiac muscle and vascular layers. Here, we summarize the evolution of biological model systems from the generation of 2D spheroids to 3D organoids by focusing on the generation of cardioids based on the currently available laboratory technologies and outline their high potential for cardiovascular research.     

Cyanobacteria,Cyanotoxins, and Neurodegenerative Diseases: Dangerous Liaisons

The prevalence of neurodegenerative disease (ND) is increasing, partly owing to extensions in lifespan, with a larger percentage of members living to an older age, but the ND aetiology and pathogenesis are not fully understood, and effective treatments are still lacking. Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are generally thought to progress as a consequence of genetic susceptibility and environmental influences. Up to now, several environmental triggers have been associated with NDs, and recent studies suggest that some cyanotoxins, produced by cyanobacteria and acting through a variety of molecular mechanisms, are highly neurotoxic, although their roles in neuropathy and particularly in NDs are still controversial. In this review, we summarize the most relevant and recent evidence that points at cyanotoxins as environmental triggers in NDs development.     

Plant Growth Promotion Function of Bacillus sp. Strains Isolated from Salt-Pan Rhizosphere and Their Biocontrol Potential against Macrophomina phaseolina

In recent decades, intensive crop management has involved excessive use of pesticides or fertilizers, compromising environmental integrity and public health. Accordingly, there has been worldwide pressure to find an eco-friendly and safe strategy to ensure agricultural productivity. Among alternative approaches, Plant Growth-Promoting (PGP) rhizobacteria are receiving increasing attention as suitable biocontrol agents against agricultural pests. In the present study, 22 spore-forming bacteria were selected among a salt-pan rhizobacteria collection for their PGP traits and their antagonistic activity against the plant pathogen fungus Macrophomina phaseolina. Based on the higher antifungal activity, strain RHFS10, identified as Bacillus vallismortis, was further examined and cell-free supernatant assays, column purification, and tandem mass spectrometry were employed to purify and preliminarily identify the antifungal metabolites. Interestingly, the minimum inhibitory concentration assessed for the fractions active against M. phaseolina was 10 times lower and more stable than the one estimated for the commercial fungicide pentachloronitrobenzene. These results suggest the use of B. vallismortis strain RHFS10 as a potential plant growth-promoting rhizobacteria as an alternative to chemical pesticides to efficiently control the phytopathogenic fungus M. phaseolina.     

The AFLATOX® Project: Approaching the Development of New Generation,Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox^® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem.     

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.     

Sounds Stimulation on In Vitro HL1 Cells: A Pilot Study and a Theoretical Physical Model

Mechanical vibrations seem to affect the behaviour of different cell types and the functions of different organs. Pressure waves, including acoustic waves (sounds), could affect cytoskeletal molecules via coherent changes in their spatial organization and mechano-transduction signalling. We analyzed the sounds spectra and their fractal features. Cardiac muscle HL1 cells were exposed to different sounds, were stained for cytoskeletal markers (phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1), and studied with multifractal analysis (using FracLac for ImageJ). A single cell was live-imaged and its dynamic contractility changes in response to each different sound were analysed (using Musclemotion for ImageJ). Different sound stimuli seem to influence the contractility and the spatial organization of HL1 cells, resulting in a different localization and fluorescence emission of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the fractal structure of the sound used, we speculate that it can influence the cells by virtue of the different sound waves’ geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our results, based on the coherent molecular dynamics. We stress the role of the systemic view in the understanding of the biological activity.     

How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease

Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.     

Experimental methods in chemical engineering: X‐ray photoelectron spectroscopy‐XPS

X‐ray photoelectron spectroscopy (XPS) is a quantitative surface analysis technique used to identify the elemental composition, empirical formula, chemical state, and electronic state of an element. The kinetic energy of the electrons escaping from the material surface irradiated by an x‐ray beam produces a spectrum. XPS identifies chemical species and quantifies their content and the interactions between surface species. It is minimally destructive and is sensitive to a depth between 1–10nm. The elemental sensitivity is in the order of 0.1 atomic %. It requires ultra high vacuum ( Pa) in the analysis chamber and measurement time varies from minutes to hours per sample depending on the analyte. XPS dates back 50 years ago. New spectrometers, detectors, and variable size photon beams, reduce analysis time and increase spatial resolution. An XPS bibliometric map of the 10 000 articles indexed by Web of Science^[1] identifies five research clusters: (i) nanoparticles, thin films, and surfaces; (ii) catalysis, oxidation, reduction, stability, and oxides; (iii) nanocomposites, graphene, graphite, and electro‐chemistry; (iv) photocatalysis, water, visible light, and ; and (v) adsorption, aqueous solutions, and waste water.