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Background: Patients with chronic kidney disease (CKD) have an increased cardiovascular (CV) risk. The lower the glomerular filtration rate, the higher the CV risk., Summary: Current data suggest that several uremic toxins lead to vascular inflammation and oxidative stress that, in turn, lead to endothelial dysfunction, changes in smooth muscle cells' phenotype, and increased degradation of elastin and collagen fibres. These processes lead to both functional and structural arterial stiffening and explain part of the increased risk of acute myocardial infarction and stroke reported in patients with CKD. Considering that, at least in patients with end-stage kidney disease, the reduction of arterial stiffness is associated with a parallel decrease of the CV risk, vascular function is a potential target for therapy to reduce the CV risk., Key Messages: in this review, we explore mechanisms of vascular dysfunction in CKD, paying particular attention to inflammation, reporting current data in other models of mild and severe inflammation, and discussing the vascular effect of several drugs currently used in nephrology., (The Author(s). Published by S. Karger AG, Basel.)

Objectives: To assess the reversibility of retinal microvascular changes in the long term and to investigate the potential links with other vascular diseases of COVID-19., Methods: We designed a prospective multicenter observational study. Patients were enrolled from the Methuselah study cohort. Retinal vascular function was studied in these patients using optical coherence tomography angiography (OCTA); aortic stiffness was measured using aortic pulse wave velocity. These examinations were performed 1 (Visit 1) and 12 (Visit 2) months after the hospital discharge for severe COVID-19. A control subject group matched for age and sex was included to define normal values., Results: A total of 28 control subjects (56 eyes) and 25 patients (50 eyes) completed the scheduled OCTA assessment; 18 patients (36 eyes) also completed the macrovascular examination. Compared to controls, the vessel density of the superficial capillary plexus (SCP) was reduced, whereas the foveal avascular zone area was enlarged at Visit 1 ( p  = 0.016 and < 0.001, respectively) and was not modified after the 12-month follow-up in COVID-19 patients ( p  = 0.011 and 0.001, respectively). Higher inflammation and lower renal function during hospitalization were linked to higher aortic stiffness and reduced vessel density of the SCP 1 month after the acute phase of COVID-19. A slower recovery of aortic dysfunction was linked to worse retinal vascular outcomes at Visit 2., Conclusion: Retinal vascular alterations were not reversible 12 months after COVID-19 and were linked to inflammation and renal dysfunction during hospitalization as well as to aortic stiffness measured during follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Castellino, Longo, Russo, Bonfiglio, Fallico, Toro, Cappellani, Grillo, Gaudio, Lo Cicero, Sessa, Colaci, Malatino, Castellino, Avitabile and Zanoli.)

Background: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV)., Methods: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks., Results: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25-48) weeks after COVID-19 onset, and they had higher carotid Young's elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P =0.04). Moreover, aPWV (path coefficient: -0.186; P =0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (-9%; P =0.01), incremental Young's elastic modulus (-17%; P =0.03), baroreflex sensitivity (+28%; P =0.049), heart rate variability triangular index (+15%; P =0.01), and subendocardial viability ratio (+12%; P =0.01×10 -4 ) were significantly improved. There was a trend toward improvement in brachial PWV (-6%; P =0.14) and carotid distensibility (+18%; P =0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P =0.04) remained significantly higher in patients with COVID-19 than in control subjects., Conclusions: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

The glutathione transferases (GSTs) are members of a superfamily of enzymes with pivotal role in the detoxification of both xenobiotic and endogenous compounds. In this work, the generation and characterization of transgenic tobacco plants over-expressing tau glutathione transferases from Citrus sinensis (CsGSTU1 and CsGSTU2) and several cross-mutate forms of these genes are reported. Putative transformed plants were verified for the presence of the transgenes and the relative quantification of transgene copy number was evaluated by Taqman real time PCR. The analysis of gene expression revealed that transformed plants exhibit high levels of CsGSTU transcription suggesting that the insertion of the transgenes occurred in transcriptional active regions of the tobacco genome. In planta studies demonstrate that transformed tobacco plants gain tolerance against fluorodifen. Simultaneously, the wild type CsGSTU genes were in vitro expressed and their kinetic properties were determined using fluorodifen as substrate. The results show that CsGSTU2 follows a Michaelis-Menten hyperbolic kinetic, whereas CsGSTU1 generates a sigmoid plot typical of the regulatory enzymes, thus suggesting that when working at sub-lethal fluorodifen concentrations CsGSTU2 can counteract the herbicide injury more efficiently than the CsGSTU1. Moreover, the transgenic tobacco plant over-expressing CsGSTs exhibited both drought and salinity stress tolerance. However, as we show that CsGSTUs do not function as glutathione peroxidase in vitro, the protective effect against salt and drought stress is not due to a direct scavenging activity of the oxidative stress byproducts. The transgenic tobacco plants, which are described in the present study, can be helpful for phytoremediation of residual xenobiotics in the environment and overall the over-expression of CsGSTUs can be helpful to develop genetically modified crops with high resistance to abiotic stresses., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The use of plants to reclaim contaminated soils and groundwater, known as phytoremediation, is a promising biotechnological strategy which has gained a lot of attention in the last few years. Plants have evolved sophisticated detoxification systems against the toxin chemicals: following the uptake, the compounds are activated so that certain functional groups can conjugate hydrophilic molecules, such as thiols. The resulting conjugates are recognized by the tonoplast transporters and sequestered into the vacuoles. The xenobiotic conjugation with glutathione is mediated by enzymes which belong to the superfamily of glutathione S-transferases (GSTs) catalyzing the nucleophylic attack of the sulphur of glutathione on the electrophilic groups of the cytotoxic substrates therefore playing a crucial role in their degradation. This study was designed to identify the putative correlation between structural and functional characteristics of plant GST classes belonging to different plant species. Consequently, the protein sequences of the expressed GSTs have been retrieved from UniGene, classified and then analyzed in order to assess the evolutionary trend and to predict secondary structure. Moreover, the fingerprint analysis was performed with SCAN Prosite in the attempt to correlate meaningful signature profile and biological information. The results evidenced that all the soluble GSTs have a tendency to assume the α-helix secondary structure followed by random coil and β-sheet. The fingerprint analysis revealed that specific signature profiles related mainly to protein phosphorylation are in the GST classes of all considered species thus suggesting that they might be subjected to reversible activation by phosphorylation-mediated regulation. This approach provides the knowledge of the relationship between presence of conserved signature profile and biological function in the view of future selection of GSTs which might be employed in either mutagenesis or genetic engineering studies.

The health benefits associated with the consumption of anthocyanin-containing foods are extensively documented. Mature fruits of blood oranges and their hybrids are characterized by the presence of these bioactive pigments, the abundance of which can be enhanced by storing fruit at cooling nonfreezing temperature. In this work the effects of short low-temperature exposure (4 °C × 15 days) upon orange anthocyanin content and the expression of structural genes belonging to the pigment biosynthesis pathway were investigated. The results highlight that anthocyanin levels of fruit exposed to cold sharply increase, reaching, after 6 days of storage, a value 8 times higher than that observed in the time zero samples, thus suggesting that fruit with enhanced health-related attributes might be obtained at this storage stage. The analysis of gene expression shows that the amount of transcripts of all considered genes (CM1, PAL, CHS, DFR, ANS, UFGT, and GST) sharply increased after 3-6 days of cold storage, confirming previous data showing that the biosynthesis of anthocyanins is a cold-regulated pathway. By comparing the expression of selected genes (PAL, DFR, and UFGT) between blood and common oranges, it turns out that those genes strictly involved in anthocyanin biosynthesis are not cold responsive in common oranges. Moreover, the data highlight that the EST encoding the transcription factor NAC domain protein is selectively induced by cold in blood oranges but not in common oranges, thus proposing it as a candidate gene specifically involved in blood orange response to cold exposure.