Search

Olga Baraldi,1 Francesca Bianchi,2,3 Viola Menghi,1 Andrea Angeletti,1 Anna Laura Croci Chiocchini,1 Maria Cappuccilli,1 Valeria Aiello,1 Giorgia Comai,1 Gaetano La Manna1 1Department of Experimental, Diagnostic and Specialty Medicine, Nephrology, Dialysis and Renal Transplant Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, 2Stem Wave Institute for Tissue Healing, Gruppo Villa Maria Care & Research – Ettore Sansavini Health Science Foundation, Lugo, Ravenna, 3National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy Background: Acute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress.Materials and methods: Lactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9) and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide.Results: HB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9.Conclusion: This in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling. Keywords: acute kidney injury, apoptosis, hyaluronan ester of butyric acid, mesangial cells

Abstract The discovery of ambient superconductivity would mark an epochal breakthrough long-awaited for over a century, potentially ushering in unprecedented scientific and technological advancements. The recent findings on high-temperature superconducting phases in various hydrides under high pressure have ignited optimism, suggesting that the realization of near-ambient superconductivity might be on the horizon. However, the preparation of hydride samples tends to promote the emergence of various metastable phases, marked by a low level of experimental reproducibility. Identifying these phases through theoretical and computational methods entails formidable challenges, often resulting in controversial outcomes. In this paper, we consider N-doped LuH3 as a prototypical complex hydride: By means of machine-learning-accelerated force-field molecular dynamics, we have identified the formation of H2 molecules stabilized at ambient pressure by nitrogen impurities. Importantly, we demonstrate that this molecular phase plays a pivotal role in the emergence of a dynamically stable, low-temperature, experimental-ambient-pressure superconductivity. The potential to stabilize hydrogen in molecular form through chemical doping opens up a novel avenue for investigating disordered phases in hydrides and their transport properties under near-ambient conditions.

Abstract Brain and breathing activities are closely related. However, the exact neurophysiological mechanisms that couple the brain and breathing to stimuli in the external environment are not yet agreed upon. Our data support that synchronization and dynamic attunement are two key mechanisms that couple local brain activity and breathing to external periodic stimuli. First, we review the existing literature, which provides strong evidence for the synchronization of brain and breathing in terms of coherence, cross-frequency coupling and phase-based entrainment. Second, using EEG and breathing data, we show that both the lungs and localized brain activity at the Cz channel attune the temporal structure of their power spectra to the periodic structure of external auditory inputs. We highlight the role of dynamic attunement in playing a key role in coordinating the tripartite temporal alignment of localized brain activity, breathing and input dynamics across longer timescales like minutes. Overall, this perspective sheds light on potential mechanisms of brain-breathing coupling and its alignment to stimuli in the external environment.

Abstract In this study we examine the impact of cell confluency on gene expression. We focused on Argonaute (AGO) protein dynamics and associated gene and protein expression in HEK293, A375, and SHSY5Y cell lines. As a consequence of cell confluency, AGO2 protein translocates into the nucleus. Therefore, we generated transcriptomic data using RNA sequencing to compare gene expression in subconfluent versus confluent cells, which highlighted significant alterations in gene regulation patterns directly corresponding to changes in cell density. Our study also encompasses miRNA profiling data obtained through small RNA sequencing, revealing miRNA expressional changes dependent on cellular confluency, as well as cellular localization. Finally, we derived proteomic data from mass spectrometry analyses following AGO1-4 immunoprecipitation, providing a comprehensive view of AGO interactome in both nuclear and cytoplasmic compartments under varying confluency. These datasets offer a detailed exploration of the cellular and molecular dynamics, influenced by cell confluency, presenting a valuable resource for further research in cellular biology, particularly in understanding the basic mechanisms of cell density in cancer cells.

The present study was conducted to investigate the effects of fish meal (FM) replacement with full fat Hermetia illucens (HI) on the molecular mechanisms regulating lipid and bile salt (BA) homeostasis in rainbow trout (Oncorhynchus mykiss) juveniles. We thus explore the presence of 20-hydroxyecdysone (20E) in an insect meal-based diet and evaluate its potential involvement in regulating the molecular mechanisms/basis of FXR:RXR axis signaling. Ecdysteroids are a category of steroid hormones which bind a nuclear–receptor complex composed of ecdysone receptor (EcR) and ultraspiracle protein (USP) and regulate insect molting and metamorphosis. In all vertebrates, including fish, EcR-USP homologs are the Farnesoid X receptors (FXR) and the Retinoid X receptors (RXR), which are known to regulate crucial physiological and metabolic aspects, including BA synthesis and cholesterol homeostasis. In silico prediction indicates that 20E binds the heterodimeric complex with a binding affinity constant Kd equals to 610 ± 60 nM and affects positively the dimerization process. Results also demonstrated the coordinated increased expression of FXR and RXR, as well as their downstream target genes (i.e. short heterodimer partner 1 and 2) in rainbow trout fed diets containing HI meal. This latter finding was paralleled by a significant down-regulation of CYP7a1 and CYP8b1 gene expression together with a decrease in hepatic total cholesterol, triglyceride, and BA levels. Overall, our study suggested that FXR is a potential target for 20E content in insect meal and provided preliminary data on the potential role of ecdysteroids in regulating the metabolic status of teleost fish through modulation of FXR signaling in the enterohepatic system.

Microplastics (MPs) accumulate in tissues, including kidney tissue, while Bisphenol A (BPA) is a plasticizer of particular concern. At present, the combined effects of MPs and BPA are unexplored in human renal cells. Therefore, we exposed a proximal tubular cell line (PTECs) to polyethylene (PE)-MPs and BPA, both separately and in combination. When co-exposed, cells showed a significantly reduced cell viability (MTT test) and a pronounced pro-oxidant (MDA levels, NRF2 and NOX4 expression by Western blot) and pro-inflammatory response (IL1β, CCL/CCR2 and CCL/CCR5 mRNAs by RT-PCR), compared to those treated with a single compound. In addition, heat shock protein (HSP90), a chaperone involved in multiple cellular functions, was reduced (by Western Blot and immunocytochemistry), while aryl hydrocarbon receptor (AHR) expression, a transcription factor which binds environmental ligands, was increased (RT-PCR and immunofluorescence). Our research can contribute to the study of the nephrotoxic effects of pollutants and MPs and shed new light on the combined effects of BPA and PE-MPs.

Ibrutinib, a highly effective inhibitor of the Bruton tyrosine kinase, has significantly transformed the therapeutic approach in chronic lymphocytic leukemia (CLL). Despite these advancements, the disease continues to be characterized by immune dysfunction and increased susceptibility to infections, with mortality rates from infections showing no significant improvement over the past few decades. Therefore, timely prevention, recognition, and treatment of infections remains an important aspect of the standard management of a patient with CLL. A panel of hematologists with expertise in CLL met to discuss existing literature and clinical insights for the management of infectious in CLL undergoing ibrutinib treatment. Despite not being a fully comprehensive review on the topic, this work provides a set of practical recommendations that can serve as a guide to healthcare professionals who manage these patients in their daily clinical practice.

Abstract Purpose Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) frequently exhibit Non-Suicidal Self-Injury (NSSI), yet their co-occurrence is still unclear. To address this issue, the aim of this study was to elucidate the role of impairments in interoception in explaining the NSSI phenomenon in AN and BN, providing an explanatory model that considers distal (insecure attachment/IA and traumatic childhood experiences/TCEs) and proximal (dissociation and emotional dysregulation) risk factors for NSSI. Method 130 patients with AN and BN were enrolled and administered self-report questionnaires to assess the intensity of NSSI behaviors, interoceptive deficits, IA, TCEs, emotional dysregulation and dissociative symptoms. Results Results from structural equation modeling revealed that impairments in interoception acted as crucial mediators between early negative relational experiences and factors that contribute to NSSI in AN and BN, particularly emotional dysregulation and dissociation. Precisely, both aspects of IA (anxiety and avoidance) and various forms of TCEs significantly exacerbated interoceptive deficits, which in turn are associated to the emergence of NSSI behaviors through the increase in levels of dissociation and emotional dysregulation. Conclusions The proposed model provided a novel explanation of the occurrence of NSSIs in patients with AN and BN by accounting for the significance of interoception. Level of evidence: Level V–Cross-sectional observational study.

This article reports on the inclusive production cross section of several quarkonium states, J / ψ, ψ(2 S) , Υ (1 S) , Υ (2 S) , and Υ (3 S) , measured with the ALICE detector at the LHC, in pp collisions at s=5.02 TeV. The analysis is performed in the dimuon decay channel at forward rapidity (2.5 < y< 4). The integrated cross sections and transverse-momentum (pT) and rapidity (y) differential cross sections for J / ψ, ψ(2 S) , Υ (1 S) , and the ψ(2 S) -to-J / ψ cross section ratios are presented. The integrated cross sections, assuming unpolarized quarkonia, are: σJ/ψ (pT< 20 GeV/c) = 5.88 ± 0.03 ± 0.34μb, σψ(2S) (pT< 12 GeV/c) = 0.87 ± 0.06 ± 0.10μb, σΥ(1S) (pT< 15 GeV/c) = 45.5 ± 3.9 ± 3.5 nb, σΥ (2 S) (pT< 15 GeV/c) = 22.4 ± 3.2 ± 2.7 nb, and σΥ (3 S) (pT< 15 GeV/c) = 4.9 ± 2.2 ± 1.0 nb, where the first (second) uncertainty is the statistical (systematic) one. For the first time, the cross sections of the three Υ states, as well as the ψ(2 S) one as a function of pTand y, are measured at s=5.02 TeV at forward rapidity. These measurements also significantly extend the J / ψpTreach and supersede previously published results. A comparison with ALICE measurements in pp collisions at s=2.76, 7, 8, and 13 TeV is presented and the energy dependence of quarkonium production cross sections is discussed. Finally, the results are compared with the predictions from several production models.

α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

Antivirulence agents are considered a promising strategy to treat bacterial infections. Fluoropyrimidines possess antivirulence and antibiofilm activity against Gram-negative bacteria; however, their mechanism of action is yet unknown. Consistent with their known antibiofilm activity, fluoropyrimidines, particularly 5-fluorocytosine (5-FC), impair curli-dependent surface adhesion by Escherichia coli MG1655 via downregulation of curli fimbriae gene transcription. Curli inhibition requires fluoropyrimidine conversion into fluoronucleotides and is not mediated by c-di-GMP or the ymg-rcs envelope stress response axis, previously suggested as the target of fluorouracil antibiofilm activity in E. coli. In contrast, 5-FC hampered the transcription of curli activators RpoS and stimulated the expression of Fis, a curli repressor affected by nucleotide availability. This last observation suggested a possible perturbation of the de novo pyrimidine biosynthesis by 5-FC: indeed, exposure to 5-FC resulted in a ca. 2-fold reduction of UMP intracellular levels while not affecting ATP. Consistently, expression of the de novo pyrimidine biosynthesis genes carB and pyrB was upregulated in the presence of 5-FC. Our results suggest that the antibiofilm activity of fluoropyrimidines is mediated, at least in part, by perturbation of the pyrimidine nucleotide pool. We screened a genome library in search of additional determinants able to counteract the effects of 5-FC. We found that a DNA fragment encoding the unknown protein D8B36_18,480 and the N-terminal domain of the penicillin-binding protein 1b (PBP1b), involved in peptidoglycan synthesis, could restore curli production in the presence of 5-FC. Deletion of the PBP1b-encoding gene mrcB, induced csgBAC transcription, while overexpression of the gene encoding the D8B36_18,480 protein obliterated its expression, possibly as part of a coordinated response in curli regulation with PBP1b. While the two proteins do not appear to be direct targets of 5-FC, their involvement in curli regulation suggests a connection between peptidoglycan biosynthesis and curli production, which might become even more relevant upon pyrimidine starvation and reduced availability of UDP-sugars needed in cell wall biosynthesis. Overall, our findings link the antibiofilm activity of fluoropyrimidines to the redirection of at least two global regulators (RpoS, Fis) by induction of pyrimidine starvation. This highlights the importance of the de novo pyrimidines biosynthesis pathway in controlling virulence mechanisms in different bacteria and makes the pathway a potential target for antivirulence strategies.

Correlations between mean transverse momentum [pT] and anisotropic flow coefficients v2 or v3 are measured as a function of centrality in Pb–Pb and Xe–Xe collisions at sNN=5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pT], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTo initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTo based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTo initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pT] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state and help pin down the uncertainty of the extracted properties of the quark–gluon plasma recreated in relativistic heavy-ion collisions.

The interaction of Λ and Σ hyperons (Y) with nucleons (N) is strongly influenced by the coupled-channel dynamics. Due to the small mass difference of the NΛ and NΣ systems, the sizable coupling strength of the NΣ↔NΛ processes constitutes a crucial element in the determination of the NΛ interaction. In this letter we present the most precise measurements on the interaction of pΛ pairs, from zero relative momentum up to the opening of the NΣ channel. The correlation function in the relative momentum space for pΛ⊕p‾Λ‾ pairs measured in high-multiplicity triggered pp collisions at s=13 TeV at the LHC is reported. The opening of the inelastic NΣ channels is visible in the extracted correlation function as a cusp-like structure occurring at relative momentum k⁎=289MeV/c. This represents the first direct experimental observation of the NΣ↔NΛ coupled channel in the pΛ system. The correlation function is compared with recent chiral effective field theory calculations, based on different strengths of the NΣ↔NΛ transition potential. A weaker coupling, as possibly supported by the present measurement, would require a more repulsive three-body NNΛ interaction for a proper description of the Λ in-medium properties, which has implications on the nuclear equation of state and for the presence of hyperons inside neutron stars.

First measurements of balance functions (BFs) of all combinations of identified charged hadron (π,K,p) pairs in Pb–Pb collisions at sNN=2.76 TeV recorded by the ALICE detector are presented. The BF measurements are carried out as two-dimensional differential correlators versus the relative rapidity (Δy) and azimuthal angle (Δφ) of hadron pairs, and studied as a function of collision centrality. The Δφ dependence of BFs is expected to be sensitive to the light quark diffusivity in the quark–gluon plasma. While the BF azimuthal widths of all pairs substantially decrease from peripheral to central collisions, the longitudinal widths exhibit mixed behaviors: BFs of ππ and cross-species pairs narrow significantly in more central collisions, whereas those of KK and pp are found to be independent of collision centrality. This dichotomy is qualitatively consistent with the presence of strong radial flow effects and the existence of two stages of quark production in relativistic heavy-ion collisions. Finally, the first measurements of the collision centrality evolution of BF integrals are presented, with the observation that charge balancing fractions are nearly independent of collision centrality in Pb–Pb collisions. Overall, the results presented provide new and challenging constraints for theoretical models of hadron production and transport in relativistic heavy-ion collisions.

The production of K∗(892)0 and φ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at sNN = 5.02 TeV has been measured using the ALICE detector at the Large Hadron Collider (LHC). The transverse momentum (pT) distributions of K∗(892)0 and φ(1020) mesons have been measured at midrapidity (|y| 8 GeV/c, the RAA values of K∗(892)0 and φ(1020) are below unity and observed to be similar to those of pions, kaons, and (anti)protons. The RAA values at high pT (>8 GeV/c) for K∗(892)0 and φ(1020) mesons are in agreement within uncertainties for sNN= 5.02 and 2.76 TeV.

Vaccines represent the most important medical evolution in the last two centuries allowing prevention and formally eradication of a wide number of infectious diseases. Safety and effectiveness are main issues that still require an open discussion. A few clinical reports described a critical temporal relationship between vaccination and acute nephrotic syndrome, indirectly suggesting an association. For this review, the literature was reviewed to identify articles reporting associations of nephrotic syndrome with vaccines against a vast array of infectious diseases (including bacteria, virus and Sars-Cov-2). As specific aims, we evaluated effectiveness and safety in terms of occurrence of either 'de novo' nephrotic syndrome in health subjects or 'relapse' in those already affected by the disease. In total, 377 articles were found; 166 duplicates and 71 non-full text, animal studies or non-English language were removed. After excluding another 50 articles not containing relevant data on generic side effects or on relapses or new onset nephrotic syndrome, 90 articles met the search criteria. Overall, studies reported the effect of vaccines in 1015 patients, plus 4 nationwide epidemiologic investigations. Limited experience on vaccination of NS patients with measles, mumps, and rubella live attenuated vaccines does not allow any definitive conclusion on their safeness. VZV has been administered more frequently without side effects. Vaccines utilizing virus inactivated, recombinant, and toxoid can be utilized without risks in NS. Vaccines for influenza reduce the risk of infections during the pandemic and are associated with reduced risk of relapse of NS typically induced by the infection. Vaccines for SARS-CoV-2 (all kinds) offer a concrete approach to reduce the pandemic. 'De novo' NS or recurrence are very rare and respond to common therapies., Author(s): Andrea Angeletti [sup.1] , Francesca Lugani [sup.1] , Edoardo La Porta [sup.1] , Enrico Verrina [sup.1] , Gianluca Caridi [sup.1] , Gian Marco Ghiggeri [sup.1] Author Affiliations: (1) grid.419504.d, [...]