The adipokines in cancer cachexia

Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The hallmark of cancer cachexia is an extended weight loss mainly due to skeletal muscle wasting and fat storage depletion from adipose tissue. The latter exerts key functions for the health of the whole organism, also through the secretion of several adipokines. These hormones induce a plethora of effects in target tissues, ranging from metabolic to differentiating ones. Conversely, the decrease of the circulating level of several adipokines positively correlates with insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. A lot of findings suggest that cancer cachexia is associated with changed secretion of adipokines by adipose tissue. In agreement, cachectic patients show often altered circulating levels of adipokines. This review reported the findings of adipokines (leptin, adiponectin, resistin, apelin, and visfatin) in cancer cachexia, highlighting that to study in-depth the involvement of these hormones in this pathology could lead to the development of new therapeutic strategies

Predictive maintenance: a novel framework for a data-driven, semi-supervised, and partially online prognostic health management application in industries

Prognostic Health Management (PHM) is a predictive maintenance strategy, which is based on Condition Monitoring (CM) data and aims to predict the future states of machinery. The existing literature reports the PHM at two levels: methodological and applicative. From the methodological point of view, there are many publications and standards of a PHM system design. From the applicative point of view, many papers address the improvement of techniques adopted for realizing PHM tasks without covering the whole process. In these cases, most applications rely on a large amount of historical data to train models for diagnostic and prognostic purposes. Industries, very often, are not able to obtain these data. Thus, the most adopted approaches, based on batch and off-line analysis, cannot be adopted. In this paper, we present a novel framework and architecture that support the initial application of PHM from the machinery producers’ perspective. The proposed framework is based on an edge-cloud infrastructure that allows performing streaming analysis at the edge to reduce the quantity of the data to store in permanent memory, to know the health status of the machinery at any point in time, and to discover novel and anomalous behaviors. The collection of the data from multiple machines into a cloud server allows training more accurate diagnostic and prognostic models using a higher amount of data, whose results will serve to predict the health status in real-time at the edge. The so-built PHM system would allow industries to monitor and supervise a machinery network placed in different locations and can thus bring several benefits to both machinery producers and users. After a brief literature review of signal processing, feature extraction, diagnostics, and prognostics, including incremental and semi-supervised approaches for anomaly and novelty detection applied to data streams, a case study is presented. It was conducted on data collected from a test rig and shows the potential of the proposed framework in terms of the ability to detect changes in the operating conditions and abrupt faults and storage memory saving. The outcomes of our work, as well as its major novel aspect, is the design of a framework for a PHM system based on specific requirements that directly originate from the industrial field, together with indications on which techniques can be adopted to achieve such goals

Editorial: Source or sink? Erosional and depositional signatures of tectonic activity in deep-sea sedimentary systems

Funding Information: We sincerely thank all the authors and reviewers who have participated in this Research Topic.Peer reviewedPublisher PD

The effects of two gold-N-heterocyclic carbene (NHC) complexes in ovarian cancer cells: a redox proteomic study

Purpose: Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Standard treatment consists of tumor debulking surgery followed by platinum and paclitaxel chemotherapy; yet, despite the initial response, about 70-75% of patients develop resistance to chemotherapy. Gold compounds represent a family of very promising anticancer drugs. Among them, we previously investigated the cytotoxic and pro-apoptotic properties of Au(NHC) and Au(NHC)2PF6, i.e., a monocarbene gold(I) complex and the corresponding bis(carbene) complex. Gold compounds are known to alter the redox state of cells interacting with free cysteine and selenocysteine residues of several proteins. Herein, a redox proteomic study has been carried out to elucidate the mechanisms of cytotoxicity in A2780 human ovarian cancer cells. Methods: A biotinylated iodoacetamide labeling method coupled with mass spectrometry was used to identify oxidation-sensitive protein cysteines. Results: Gold carbene complexes cause extensive oxidation of several cellular proteins; many affected proteins belong to two major functional classes: carbohydrate metabolism, and cytoskeleton organization/cell adhesion. Among the affected proteins, Glyceraldehyde-3-phosphate dehydrogenase inhibition was proved by enzymatic assays and by ESI-MS studies. We also found that Au(NHC)2PF6 inhibits mitochondrial respiration impairing complex I function. Concerning the oxidized cytoskeletal proteins, gold binding to the free cysteines of actin was demonstrated by ESI-MS analysis. Notably, both gold compounds affected cell migration and invasion. Conclusions: In this study, we deepened the mode of action of Au(NHC) and Au(NHC)2PF6, identifying common cellular targets but confirming their different influence on the mitochondrial function

Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780)

The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were investigated through a strategy based on simultaneous expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, metabolic changes associated with conversion to a glycolytic phenotype, induction of ER stress. The occurrence of the above cellular changes was extensively validated by performing direct biochemical assays. Our data are consistent with the concept that AF produces its effects through a multitarget mechanism that mainly affects the redox metabolism and the mitochondrial functions and results into severe ER stress. Results are discussed in the context of the current mechanistic knowledge existing on AF

Proteomic and carbonylation profile analysis of rat skeletal muscles following acute swimming exercise

Previous studies by us and other groups characterized protein expression variation following long-term moderate training, whereas the effects of single bursts of exercise are less known. Making use of a proteomic approach, we investigated the effects of acute swimming exercise (ASE) on protein expression and carbonylation patterns in two hind limb muscles: the Extensor Digitorum Longus (EDL) and the Soleus, mostly composed of fast-twitch and slow-twitch fibres, respectively. Carbonylation is one of the most common oxidative modifications of proteins and a marker of oxidative stress. In fact, several studies suggest that physical activity and the consequent increase in oxygen consumption can lead to increase in reactive oxygen and nitrogen species (RONS) production, hence the interest in examining the impact of RONS on skeletal muscle proteins following ASE. Results indicate that protein expression is unaffected by ASE in both muscle types. Unexpectedly, the protein carbonylation level was reduced following ASE. In particular, the analysis found 31 and 5 spots, in Soleus and EDL muscles respectively, whose carbonylation is reduced after ASE. Lipid peroxidation levels in Soleus were markedly reduced as well. Most of the decarbonylated proteins are involved either in the regulation of muscle contractions or in the regulation of energy metabolism. A number of hypotheses may be advanced to account for such results, which will be addressed in future studies

Palynofacies classification of submarine fan depositional environments: Outcrop examples from the Marnoso-Arenacea Formation, Italy

Basin floor fans contain some of the largest deep-water hydrocarbon accumulations discovered, however they also demonstrate extremely complex stratigraphic architecture, understanding of which is crucial for maximum recovery. Here we develop a new method, based upon palynofacies analysis, for the distinction of the different depositional environments that are commonly associated with basin floor fans. Previous studies and our sedimentological analysis allow good confidence in the discrimination of the different depositional environments of the outcropping Marnoso-Arenacea Formation fan system. One hundred and thirty-five samples were collected from mudstones in conjunction with sedimentary logging of 871 m of outcrops. Six lithofacies associations are described and interpreted to represent lobe axis, lobe fringe, fan fringe, contained interlobe, basin plain, and starved high depositional sub-environments. Palynofacies of these elements demonstrate turbidites to be rich in terrestrial organic matter, with sixteen categories of matter recognised. The abundances and proportions of particles varies between sub-environments, with lobe axis deposits containing the largest, densest particles, with a transition to ever smaller and lighter particles moving toward the basin plain. Fuzzy C-means statistical analysis was used to explore this trend. Distribution of organic matter is not random, but is dominated by hydrodynamic sorting and sequential fall-out of particles as turbidity currents passed across the basin. This allows a palynofacies classification scheme to be constructed to assist the identification of depositional environments of submarine fans, which may be combined with subsurface data to assist reservoir characterisation