A mixed-valence diruthenium(ii,iii) complex endowed with high stability: from experimental evidence to theoretical interpretation

We herein report the synthesis and multi-technique characterization of [Ru2Cl((2-phenylindol-3-yl)glyoxyl-l-leucine-l-phenylalanine)4], a novel diruthenium(ii,iii) complex obtained by reacting [Ru2(μ-O2CCH3)4Cl] with a dual indolylglyoxylyl dipeptide anticancer agent. We soon realised that the compound is very stable under several different conditions including aqueous buffers or organic solvents. It is also completely unreactive toward proteins. The high stability is also suggested by cellular experiments in a glioblastoma cell line. Indeed, while the parent ligand exerts high cytotoxic effects in the low μM range, the complex is completely non-cytotoxic against the same line, most probably because of the lack of ligand release. To investigate the reasons for such high stability, we carried out DFT calculations that are fully consistent with the experimental findings. The results highlight that the stability of [Ru2Cl((2-phenylindol-3-yl)glyoxyl-l-leucine-l-phenylalanine)4] relies on the nature of the ligand, including its steric hindrance that prevents the reaction of any nucleophilic group with the Ru2 core. Ligand displacement is the key step to allow reactivity with the biological targets of metal-based prodrugs. Accordingly, we discuss the implications of some important aspects that should be considered when active molecules are chosen as ligands for the synthesis of paddle-wheel-like complexes with medicinal applications. This journal i

Causal and associational language in observational health research: A systematic evaluation.

This is the final version. Available from Oxford University Press via the DOI in this record. Data, data analysis code, and materials are available on the Open Science Framework project https://osf.io/jtdaz/.We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched and screened for 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, three reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as None (no causal implication) in 13.8%, Weak 34.2%, Moderate 33.2%, and Strong 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.Marie Skłodowska-Curie grantAustralian Research CouncilNational Institute of Mental HealthNational Institute of Mental HealthNational Institute of Biomedical Imaging and BioengineeringNational Center for Advancing Translational Sciences UCLA Clinical Translational Science InstituteBloomberg American Health InitiativeKaren Toffler Charity Trus

Development of an integrated tactile sensor system for clothes manipulation and classification using industrial grippers

This paper presents the design and development of a novel tactile sensor system for clothes manipulation and perception using industrial grippers. The proposed system consists of a multi-modal tactile sensor and embedded re-programmable interface electronics. The sensing element features a matrix of capacitive pressure sensors, a microphone for acoustic measurements, and a proximity and ambient light sensor. The sensor is fully embedded and can be easily integrated at mechanical and electrical levels with industrial grippers. Tactile sensing design has been put on the same level of additional requirements, such as the mechanical interface, cable harness, and robustness against continuous and repetitive operations, just to name but a few. The performances of the different sensing modalities have been experimentally assessed using a test rig for tactile sensors and the system has been successfully integrated and tested on a real robotic gripper. Experiments have been performed in order to show the capabilities of the sensor for implementing tactile-based industrial gripper control

Strategies for the improvement of metal-based chemotherapeutic treatments

This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments

Carbonic Anhydrase Activators for Neurodegeneration: An Overview

Carbonic anhydrases (CAs) are a family of ubiquitous metal enzymes catalyzing the reversible conversion of CO2 and H2O to HCO3- with the release of a proton. They play an important role in pH regulation and in the balance of body fluids and are involved in several functions such as homeostasis regulation and cellular respiration. For these reasons, they have been studied as targets for the development of agents for treating several pathologies. CA inhibitors have been used in therapy for a long time, especially as diuretics and for the treatment of glaucoma, and are being investigated for application in other pathologies including obesity, cancer, and epilepsy. On the contrary, CAs activators are still poorly studied. They are proposed to act as additional (other than histidine) proton shuttles in the rate-limiting step of the CA catalytic cycle, which is the generation of the active hydroxylated enzyme. Recent studies highlight the involvement of CAs activation in brain processes essential for the transmission of neuronal signals, suggesting CAs activation might represent a potential therapeutic approach for the treatment of Alzheimer's disease and other conditions characterized by memory impairment and cognitive problems. Actually, some compounds able to activate CAs have been identified and proposed to potentially resolve problems related to neurodegeneration. This review reports on the primary literature regarding the potential of CA activators for treating neurodegeneration-related diseases

Histological study of the digestive tract of Sparus aurata larvae fed with different feeding regimes

During the last years, drastic reduction in the use of Artemia as a live prey for marine finfish became popular. Histological studies have been carried out regarding the distribution of mucins in the intestine of many species. In this study, the aim was to detect differences on histological level of the intestine between the different treatments, in order to understand better the role of Artemia in the development of the digestive tract. A homogeneous batch of 20days old sea bream larvae was divided into 5 different treatments, varying in the amount of Artemia that was fed and the type of dry feed used for weaning. Samples of larvae of all treatments were taken at 30, 40, 50 and 60dph for histological analyses. In all the sampled larvae goblet cells were found. No goblet cells were observed in the stomach. The number of goblet cells found is differing with the age of the larvae and differences between different individuals of the same age have been observed. This preliminary study suggests that the histological approach could be an important tool to better understand the influence of a diet on the intestine development and as a consequence on the larvae growth