Ureteral stenosis remains a significant urological complication after kidney transplantation. This study aimed to identify independent risk factors for the development of post-transplant ureteral stenosis and to evaluate their temporal impact using survival analysis in a contemporary cohort. A retrospective single-center cohort study was conducted, including 342 deceased donor kidney transplant recipients between 2014 and 2024. The primary endpoint was the time to radiologically confirmed ureteral stenosis within the first post-transplant year. Univariate analysis and Kaplan-Meier survival curves were used to identify associated factors. A multivariable Cox proportional hazards model was constructed to determine independent predictors, adjusting for clinically relevant variables. The incidence of ureteral stenosis was 11.1
Reactive oxygen species (ROS) are context-dependent mediators that function as second messengers at low, localized flux and as drivers of damage when production overruns buffering capacity. Outcomes are dictated by source identity, subcellular compartment and pulse kinetics—the “where–when–how much” rule. We synthesize advances (2015–2025) across principal generators—mitochondrial electron transport, NADPH oxidases, xanthine oxidoreductase and ER/peroxisomal oxidoreductases—to show how compartmental H2O2 microgradients encode reversible cysteine signaling, while iron-rich niches pivot chemistry toward peroxynitrite, Fenton-derived ·OH, lipid peroxidation and regulated cell death (apoptosis, ferroptosis, parthanatos). We integrate these mechanisms with endothelial dysfunction, innate immune priming, ECM remodeling and barrier failure across cardiovascular, metabolic, neurodegenerative, oncologic, pulmonary, renal and critical-illness contexts, emphasizing crosstalk with RNS/RSS and iron metabolism as key modulators. Methodologically, we advocate species-resolved, compartment-aware assessment—e.g., DHE → 2-OH-E⁺ HPLC for O2·−, targeted HyPer/roGFP-Orp for H2O2 and peroxiredoxin redox state—embedded in composite panels that pair flux with damage footprints and iron/ferroptosis metrics for attribution and trial guidance. Therapeutically, we argue against indiscriminate antioxidant loading in favor of node-specific, compartment-targeted modulation (NOX/NOS tuning, mitochondrial QC/RET tempering, ER redox control, iron/ferroptosis management, calibrated sulfur-axis support), implemented as time-staged sequences and titrated to biomarkers. Clarifying which species arise, where and when, reframes ROS from generic toxicity to precision redox modulation with translational impact.
BACKGROUND:Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) has been associated with increased stent optimization and reduced adverse events among patients with complex coronary-artery lesions, but adoption of this strategy in Western countries remains low. Although practice guidelines recommend intracoronary imaging for anatomically complex lesions, evidence from current European practice is limited. METHODS:In this investigator-initiated, international, open-label, randomized, controlled trial, we assigned patients undergoing complex PCI to either IVUS-guided PCI, performed with the use of prespecified stent-optimization criteria, or angiography-guided PCI. The primary end point was target-vessel failure, defined as a composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-vessel revascularization. RESULTS:Of the 2020 patients who underwent randomization, 1010 in the IVUS-guided PCI group and 1009 in the angiography-guided PCI group were included in the primary analysis. The mean age of the patients was 69 years, 79.4% were men, and 27.4% presented with an acute coronary syndrome. The mean procedure duration was 88.8 minutes with IVUS-guided PCI and 66.2 minutes with angiography-guided PCI. Dilation with balloon angioplasty after stent implantation was performed in 91.3% of the IVUS-guided PCI procedures and in 84.5% of the angiography-guided PCI procedures. At a median follow-up of 19.0 months (interquartile range, 15.2 to 23.4), target-vessel failure had occurred in 140 patients (13.9%) in the IVUS-guided PCI group and in 112 patients (11.1%) in the angiography-guided PCI group (hazard ratio, 1.25; 95% confidence interval, 0.97 to 1.60; P = 0.08). Procedural complications occurred in 11.3% of the IVUS-guided PCI procedures and in 10.2% of the angiography-guided PCI procedures. The frequency of adverse events appeared to be similar in the two groups. CONCLUSIONS:Among patients undergoing complex high-risk PCI, a strategy of routine IVUS-guided PCI performed with the use of prespecified stent-optimization criteria was not associated with a lower risk of target-vessel failure than angiography-guided PCI alone. (Funded by Boston Scientific; IVUS-CHIP ClinicalTrials.gov number, NCT04854070.).
Silymarin (Silybum marianum (L.) Gaertn. extract) is a widely used botanical for liver disease, yet clinical results remain inconsistent. Most mechanistic work uses supraphysiological aglycones, whereas humans are exposed predominantly to phase II conjugates that are strongly protein-bound and routed by transporters toward bile and the intestinal mucosa. We reframe silymarin activity through a spatial pharmacology lens, proposing three post-intake windows: early (0–2 h) conjugate-dominant exposure with localised β-glucuronidase-mediated reactivation; intermediate (2–8 h) enterohepatic recirculation pulses; and late (8–48 h) microbial catabolite contributions. Each window engages distinct signalling modules—Keap1/NRF2, NF-κB, and AMPK-mTOR-TFEB—via transient redox events (quinone cycling, micro-H2O2 relays) and proteostatic remodelling (autophagy/mitophagy). We synthesise human pharmacokinetic and clinical evidence—with emphasis on MASLD and alcohol-associated liver disease—and show how formulation, meal timing, and microbiome metabotype determine which windows are engaged. Finally, we propose minimum reporting standards and falsifiable hypotheses to reduce between-study heterogeneity and enable precision use of silymarin.
Cellular redox biology is governed less by bulk oxidant load than by the coupled behaviour of ROS, RNS, and RSS within spatially restricted microdomains. Within these niches, redox information is written, edited, and erased through competing post-translational modifications, including sulphenylation (-SOH), S-nitrosylation (-SNO), and persulphidation (-SSH). Local proximity to sources such as mitochondria, NOX, and NOS platforms combines with buffering by SOD and peroxidases to shape which routes dominate. Editing by thioredoxin, glutaredoxin, and GSNOR, together with sulphane sulphur flux from trans-sulphuration enzymes and mitochondrial sulphide oxidation, sets the boundary between reversible redox eustress and pathological distress dominated by peroxynitrite chemistry and irreversible oxidation. Using a compartment-aware analytical template across cardiometabolic disease, neurodegeneration, cancer, chronic inflammation, ageing, and innate immunity, we identify recurring mechanistic patterns and explain why global biomarkers can mislead. We then propose context-matched biomarker panels and therapeutic levers, with antimicrobial peptides emerging as redox-modulated effectors of innate defence within this framework. Finally, we outline precision redox pharmacology that raises local distress thresholds without flattening physiological signalling, and we propose a trial-ready agenda centred on compartment-resolved pharmacodynamic anchors.
