OBJECTIVE: Chronic kidney disease and end-stage kidney disease (ESKD) are well-established risk factors for cardiovascular disease (CVD), the leading cause of mortality in the dialysis population. Conventional therapies, such as statins, blood pressure control, and renin-angiotensin-aldosterone system blockade, have inadequately addressed this cardiovascular risk, highlighting the unmet need for effective treatment strategies. Sodium-glucose transporter 2 (SGLT2) inhibitors have demonstrated significant renal and cardiovascular benefits among patients with type 2 diabetes, heart failure, or CKD at risk of progression. Unfortunately, efficacy data in dialysis patients is lacking as ESKD was an exclusion criterion for all major clinical trials of SGLT2 inhibitors. This review explores the potential of SGLT2 inhibitors in improving cardiovascular outcomes among patients with ESKD, focusing on their direct cardiac effects.
RESULTS: Recent clinical and preclinical studies have shown promising data for the application of SGLT2 inhibitors to the dialysis population. SGLT2 inhibitors may provide cardiovascular benefits to dialysis patients, not only indirectly by preserving the remaining kidney function and improving anemia but also directly by lowering intracellular sodium and calcium levels, reducing inflammation, regulating autophagy, and alleviating oxidative stress and endoplasmic reticulum stress within cardiomyocytes and endothelial cells. This review examines the current clinical evidence and experimental data supporting the use of SGLT2 inhibitors, discusses its potential safety concerns, and outlines ongoing clinical trials in the dialysis population. Further research is needed to evaluate the safety and effectiveness of SGLT2 inhibitor use among patients with ESKD.

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Our world is made of plastic. Plastic waste deeply affects our health entering the food chain. The degradation and/or fragmentation of plastics due to weathering processes result in the generation of nanoplastics (NPs). Only a few studies tested NPs effects on human health. NPs toxic actions are, in part, mediated by oxidative stress (OS) that, among its effects, affects bone remodeling. This study aimed to assess if NPs influence skeleton remodeling through OS. Murine bone cell cultures (MC3T3-E1 preosteoblasts, MLOY-4 osteocyte-like cells, and RAW264.7 pre-osteoclasts) were used to test the NPs detrimental effects on bone cells. NPs affect cell viability and induce ROS production and apoptosis (by caspase 3/7 activation) in pre-osteoblasts, osteocytes, and pre-osteoclasts. NPs impair the migration capability of pre-osteoblasts and potentiate the osteoclastogenesis of preosteoclasts. NPs affected the expression of genes related to inflammatory and osteoblastogenic pathways in pre-osteoblasts and osteocytes, related to the osteoclastogenic commitment of pre-osteoclasts. A better understanding of the impact of NPs on bone cell activities resulting in vivo in impaired bone turnover could give more information on the possible toxicity consequence of NPs on bone mass and the subsequent public health problems, such as bone disease.

Micro and nanosize plastic polymers degrading from large plastic compounds are accumulating in the natural environment and expose potential biological threats to human health. These particles are largely persistent and consequently accumulate in the exposed individuals. The presence of microplastics has already been demonstrated in various human organs including the lung, the gastrointestinal system and the blood raising concerns about their possible harmful effects. The chemical composition, size and shape of microplastics as well as their weathering status represent important factors influencing the potential impact of microplastics on tissues. In addition, microplastics can function as vectors for adsorbed chemical compounds and may harbour and deliver live microbial pathogens or their ligands. In vitro and in vivo animal studies demonstrated that microplastics are taken up to cells in a size and cell type dependent manner. Once inside the targeted cell they activate oxidative processes, mitochondrial dysfunction and ER-stress. These molecular processes result in the activation or repression of cell type specific functions and potentially in the induction of cytotoxicity. The microplastic elicited events may result in inflammation, organ damage and fibrosis of the targeted organs as well as in systemic immunological and metabolic conditions. In addition, microplastics may impact on the gut microbiota which may exert further gastrointestinal and systemic metabolic and immunological effects. In this minireview, we evaluate the factors and mechanisms that influence potential microplastic induced cellular and organ pathologies in humans and discuss limitations of current understanding regarding microplastic elicited conditions as well as future perspectives for research.

On one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the cecal metabolome of rats. On the other side, there is also a specific and different metabolomic signature in the cecum of a strain of DCS-resistant rats, that are not exposed to hyperbaric protocol. We decide to study a conventional strain of rats that resist to an accident-provoking hyperbaric exposure, and we hypothesize that the metabolomic signature put forward may correspond to a physiological response adapted to the stress induced by diving. The aim is to verify and characterize whether the cecal compounds of rats resistant to the provocative dive have a cecal metabolomic signature different from those who do not dive. 35 asymptomatic diver rats are selected to be compared to 21 rats non-exposed to the hyperbaric protocol. Because our aim is essentially to study the differences in the cecal metabolome associated with the hyperbaric exposure, about half of the rats are fed soy and the other half of maize in order to better rule out the effect of the diet itself. Lower levels of IL-1β and glutathione peroxidase (GPX) activity are registered in blood of diving rats. No blood cell mobilization is noted. Conventional and ChemRICH approaches help the metabolomic interpretation of the 185 chemical compounds analyzed in the cecal content. Statistical analysis show a panel of 102 compounds diet related. 19 are in common with the hyperbaric protocol effect. Expression of 25 compounds has changed in the cecal metabolome of rats resistant to the provocative dive suggesting an alteration of biliary acids metabolism, most likely through actions on gut microbiota. There seem to be also weak changes in allocations dedicated to various energy pathways, including hormonal reshuffle. Some of the metabolites may also have a role in regulating inflammation, while some may be consumed for the benefit of oxidative stress management.

Objective  Sound experimental data suggest that oxidative stress plays an important role in the pathogenesis of tendinopathies. However, this hypothesis in humans remains speculative given that clinical data are lacking to confirm it. Recently, a new methodology has allowed to quantify the oxidative stress in vivo by measuring the concentration of hydroperoxides of organic compounds, which have been utilized as an oxidative stress-related marker in several pathologic and physiologic conditions. Given the reliability of this test and the lack of information in subjects with tendinopathies, the aim of the present study was to assess the oxidative stress status in elite professional soccer players with and without ultrasonographic features of tendon damage. Methods  In 73 elite players, blood metabolic parameters were evaluated and oxidative stress was measured by means of a specific test (expressed as U-Carr units). Therefore, an ultrasonographic evaluation of the Achilles and patellar tendons was performed. Results  No significant relationships were observed between metabolic parameters and oxidative stress biomarkers. The Achilles and patellar tendons showed a normal echographic pattern in 58 athletes, and sonographic abnormalities in 15. The athletes with ultrasonographic alterations, compared to those with normal US picture, showed significantly higher U-Carr levels ( p  = 0.000), body mass index (BMI) values ( p  = 0.03) and were older ( p  = 0.005). The difference in U-Carr values among the subjects remained significant also after adjustment for age and BMI. Conclusion  The results of the present study support the hypothesis that oxidative substances, also increased at systemic and not only at local level, may favor tendon damage. Level of Evidence  IV (pilot study).

Psychiatry remains in a permanent state of crisis, which fragmented psychiatry from the field of medicine. The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic, biological, molecular, pan-omics, precision, cognitive and phenomenological psychiatry, folk psychology, mind-brain dualism, descriptive psychopathology, and postpsychiatry. The current \"gold standard\" Diagnostic and Statistical Manual of Mental Disorders/International Classification of Diseases taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach. Therefore, it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches. The aim of this paper is to explain the new nomothetic network psychiatry (NNP) approach, which uses machine learning methods to build data-driven causal models of mental illness by assembling risk-resilience, adverse outcome pathways (AOP), cognitome, brainome, staging, symptomatome, and phenomenome latent scores in a causal model. The latter may be trained, tested and validated with Partial Least Squares analysis. This approach not only allows to compute pathway-phenotypes or biosignatures, but also to construct reliable and replicable nomothetic networks, which are, therefore, generalizable as disease models. After integrating the validated feature vectors into a well-fitting nomothetic network, clustering analysis may be applied on the latent variable scores of the R/R, AOP, cognitome, brainome, and phenome latent vectors. This pattern recognition method may expose new (transdiagnostic) classes of patients which if cross-validated in independent samples may constitute new (transdiagnostic) nosological categories.

We had reported that orally administered ghrelin-containing salmon stomach extract prevents doxorubicin (DOX)-induced cardiotoxicity. In this study, we investigated the binding affinity of salmon ghrelin to rat ghrelin receptor and the cardioprotective effects of subcutaneous (sc) injected synthetic salmon ghrelin in rats with DOX-induced acute heart failure in order to clarify the potential efficacy of salmon ghrelin. Intracellular calcium mobilization assay was performed on rat GHS-R1a-expressing CHO cells to reveal ghrelin activity. Rats were divided into five groups; the normal control (I), and toxic control (II) groups were given saline (sc, twice daily), and the salmon acyl-ghrelin (sAG) (III), salmon unacylated-ghrelin (sUAG) (IV), and rat acyl-ghrelin (rAG) (V) groups were given corresponding synthetic ghrelins (sc, twice daily), respectively. After seven days of treatment, DOX (20 mg/kg BW) or saline was administered to the corresponding groups by intraperitoneal injection. The toxic control group was the negative control group for the DOX-induced cardiotoxicity groups. While sAG displayed similar affinity to rAG upon application to GHS-R1a-expressing cells, and also decreased DOX-induced apoptosis and increased food intake, sUAG did not. Both sAG and rAG improved DOX-induced deterioration, showing anti-oxidative activity. The anti-oxidative activity of sAG might contribute to the protective effects on cardiomyocytes. The results also suggest that, similar to rAG, sAG is a potent protectant against DOX-induced cardiotoxicity and a potential functional component in orally administered ghrelin-containing salmon stomach extract, which prevented DOX-induced cardiotoxicity in our previous study.

Ellagitannins may have a beneficial impact in cardiovascular diseases. The aim of the study was to evaluate the effect of high-fat diet (HFD) and the efficacy of Castanea sativa Mill. bark extract (ENC) on cardiac and vascular parameters. Rats were fed with regular diet, (RD, n = 15), HFD (n = 15), RD + ENC (20 mg/kg/day by gavage, n = 15), and HFD + ENC (same dose, n = 15) and the effects on body weight, biochemical serum parameters, and inflammatory cytokines determined. Cardiac functional parameters and aorta contractility were also assessed on isolated atria and aorta. Results showed that ENC reduced weight gain and serum lipids induced by HFD. In in vitro assays, HFD decreased the contraction force of left atrium, increased right atrium chronotropy, and decreased aorta K+ -induced contraction; ENC induced transient positive inotropic and negative chronotropic effects on isolated atria from RD and HFD rats and a spasmolytic effect on aorta. In ex vivo experiments, ENC reverted inotropic and chronotropic changes induced by HFD and enhanced Nifedipine effect more on aorta than on heart. In conclusion, ENC restores metabolic dysfunction and cardiac cholinergic muscarinic receptor function, and exerts spasmolytic effect on aorta in HFD rats, highlighting its potential as nutraceutical tool in obesity.

Staphylococcus lugdunensis is a coagulase-negative Staphylococcus part of the commensal skin flora but emerge as an important opportunistic pathogen. Because iron limitation is a crucial stress during infectious process, we performed phenotypic study and compared proteomic profiles of this species incubated in absence and in presence of the iron chelator 2,2\'-dipyridyl (DIP).
No modification of cell morphology nor cell wall thickness were observed in presence of DIP. However iron-limitation condition promoted biofilm formation and reduced the ability to cope with oxidative stress (1 mM H2O2). In addition, S. lugdunensis N920143 cultured with DIP was significantly less virulent in the larvae of Galleria mellonella model of infection than that grown under standard conditions. We verified that these phenotypes were due to an iron limitation by complementation experiments with FeSO4. By mass spectrometry after trypsin digestion, we characterized the first iron-limitation stress proteome in S. lugdunensis. Among 1426 proteins identified, 349 polypeptides were differentially expressed. 222 were more and 127 less abundant in S. lugdunensis incubated in iron-limitation condition, and by RT-qPCR, some of the corresponding genes have been shown to be transcriptionally regulated. Our data revealed that proteins involved in iron metabolism and carriers were over-expressed, as well as several ABC transporters and polypeptides linked to cell wall metabolism. Conversely, enzymes playing a role in the oxidative stress response (especially catalase) were repressed.
This phenotypic and global proteomic study allowed characterization of the response of S. lugdunensis to iron-limitation. We showed that iron-limitation promoted biofilm formation, but decrease the oxidative stress resistance that may, at least in part, explained the reduced virulence of S. lugdunensis observed under low iron condition.