Chronic kidney disease (CKD) is one of the leading causes of endothelial dysfunction and directly associated with the development of cardiovascular diseases (CVD). The accumulation of uremic toxins stimulates development of an exacerbated inflammatory state, especially in the vascular endothelial microenvironment. L-carvone (CRV) monoterpene is a natural product with several described biological activities, including atheroprotective and anti-inflammatory effects. This study aimed to investigate the in vitro anti-inflammatory effect of CRV on human endothelial cells exposed to hemodialysis patients' serum.

CRV did not affect endothelial cell viability at a concentration of 100 µM, either alone or in combination with uremic serum (US), but it induced a significant increase in cell proliferation (P < 0.05). CRV significantly reduced the gene (P < 0.05) and protein (P < 0.01) expression of Interleukin (IL) 1β (IL-1β) under uremic conditions. CRV also significantly decreased protein levels of other inflammatory biomarkers such as IL-6, IL-8, vascular endothelial growth factor (VEGF-A), serum amyloid A (SAA) (P < 0.01) and tumor necrosis factor α (TNF-α) (P < 0.05) in uremic conditions. Monocyte chemoattractant protein 1 (MCP-1) production was additionally reduced (P < 0.01) and consequently monocyte migration was reduced (P < 0.05) with CRV under uremic conditions. Cell morphology appeared to remain unchanged in the presence of CRV, and it reduced the cellular damage in the uremic environment caused by uremia.

Altogether, these findings suggest the beneficial anti-inflammatory effect of CRV in the vascular environment in response to uremic damage in CKD patients, opening perspectives for the study of new targets to better understand the endothelial protection mechanisms.

Antiretroviral therapy (ART) has significantly increased life expectancy of people living with HIV (PLWH). Nonetheless, despite effective virological control, PLWH are faced with accelerated aging, characterized by higher prevalence of age-related comorbidities than the general population. Persistent inflammation and activation of innate immunity seem to drive this immunosenescent phenotype. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is increasingly recognized as a key player in the aging process and in age-related diseases, like cardiovascular and metabolic disorders, cancer, neurological diseases and cognitive decline. The human gene encoding for STING (STING1/TMEM173) exhibit significant heterogeneity, with some common single nucleotide polymorphisms (SNPs) variably affecting its immune functions (R232H and R71H, G230A, R293Q, frequently co-segregating as HAQ haplotype). This study aims to investigate the impact of those hypomorphic variants on immune control, comorbidities, and cognitive and functional outcomes in a cohort of 60 aged (> 50 years) chronic PLWH on stable ART. Patients were genotyped and differences in comorbidities, HIV-related clinical parameters, and cognitive and motor performances were assessed across genotype groups. Here we show that carriers of R71H, G230A and R293Q alleles were associated with a lower prevalence of dyslipidemia, while carriers of the R232H polymorphism show higher CD4⁺ T cell counts. Our results suggest that the common STING1/TMEM173 polymorphisms may influence immunological and clinical outcomes, modulating lipid metabolism and the dynamics of immune recovery in these people.

Phthalocyanines (Pc) have been widely employed as photosensitizers, but their rational design for application in the phototheranostics field remains challenging. Herein, a series of Pc derivatives with tunable electron-donating capabilities were designed to strengthen the intramolecular charge transfer (ICT) process. Upon the introduction of strong electron-donating substituents linked via nitrogen bridges, these complexes exhibited gradually red-shifted absorption maxima (up to 744 nm for PcMD), narrowed HOMO-LUMO gaps, quenched fluorescence emission, and promoted intersystem crossing (ISC). These favorable features consequently contributed to enhanced reactive oxygen species (ROS) generation and improved photothermal conversion efficiency. Further in vitro experiments were conducted using bovine serum albumin and folic acid co-modified PcMD (PcMD@BSA-FA). This nanoparticle exhibited strong photocytotoxicity to A375 melanoma cells upon 730 nm laser irradiation, and the corresponding half-maximal inhibitory concentration (IC₅₀) was determined to be 3.2 µM. In addition, this nanoparticle enabled concentration-dependent photoacoustic (PA) imaging, with prominent tumor accumulation reaching a maximum at 8 h post-injection. This work demonstrates that regulating the ICT process serves as an effective strategy to enhance the phototheranostic performance of Pc, and the PcMD@BSA-FA nanoparticles hold great potential for PA imaging-guided synergistic cancer phototherapy.

Spinal cord injury (SCI) triggers secondary neuroinflammatory and inflammasome-associated responses that contribute to tissue damage and functional impairment. This study evaluated nanocurcumin in experimental SCI using integrated experimental, computational, and exploratory machine-learning approaches. Adult male Wistar rats were allocated to Sham, SCI, or SCI + nanocurcumin groups. SCI was induced by T6 contusion, and nanocurcumin (50 mg/kg, intraperitoneally) was administered every 12 hours for 72 hours. Functional, histological, molecular, and inflammatory outcomes were assessed using BBB scoring, Luxol Fast Blue staining, immunofluorescence, RT-qPCR, and ELISA. SCI impaired locomotor function and myelin integrity and increased inflammasome-associated and inflammatory markers. Nanocurcumin significantly improved BBB scores, increased the LFB-positive myelinated area, and attenuated these molecular alterations. Tissue IL-1β, IL-18, HMGB1, and TLR4 levels were also reduced following nanocurcumin treatment compared with untreated SCI. Correlation and hierarchical clustering analyses demonstrated coordinated molecular-functional associations and separation of SCI from control and treated profiles. Exploratory Random Forest/SHAP analyses highlighted NF-κB, Caspase-1, NOX2, and NLRP3 as influential variables for group discrimination. Docking predicted favorable curcumin-target interactions, while MD simulations supported distinct conformational behavior of selected complexes. Overall, nanocurcumin was associated with attenuated inflammatory and inflammasome-associated responses and improved early functional and histological outcomes following SCI.

Congenital heart disease (CHD) patients increasingly survive into adulthood, yet chronic kidney disease (CKD) is common. End-stage renal disease management is challenging due to hemodynamic instability and perioperative risks. Renal transplantation may improve survival and function, but outcomes are poorly characterized.

To evaluate graft and patient survival, complications, and clinical considerations in pediatric and adult CHD patients undergoing renal transplantation.

A PRISMA-compliant systematic review was conducted across PubMed, Embase, Cochrane, Scopus, and Google Scholar through September 2025. Studies reporting renal transplantation outcomes in pediatric or adult CHD populations were included. Data extraction covered study characteristics, demographics, graft and patient survival, complications, and follow-up. Risk of bias was assessed using Joanna Briggs Institute and Newcastle-Ottawa tools. Narrative synthesis was performed.

Seventeen studies (12 case reports, 4 retrospective cohorts, 1 case series) including pediatric (1.2-18 years) and adult (up to 54 years) CHD patients were analyzed. Graft survival was generally favorable, with preserved renal function in most patients. Patient survival was high and comparable to non-CHD recipients, though complex CHD increased perioperative risk. Perioperative complications included prolonged ventilation, transfusion requirements, and extended hospitalization. Urological complications were common, while acute rejection and delayed graft function were infrequent. Cardiovascular events were rare. Multidisciplinary perioperative management improved outcomes.

Renal transplantation is feasible and effective in pediatric and adult CHD populations. Careful patient selection and multidisciplinary care yield high graft and patient survival despite increased perioperative complexity.

BackgroundUnfractionated heparin (UFH) is widely used in non-ST-segment elevation myocardial infarction (NSTEMI), but its narrow therapeutic window requires frequent activated partial thromboplastin time (aPTT) monitoring. Data on time in therapeutic range (TTR) in this setting are scarce.MethodsWe analyzed 1,553 consecutive patients with NSTEMI treated with UFH in a tertiary care intensive cardiovascular care unit between July 2019 and December 2025. TTR was calculated by linear interpolation over 72 hours. Associations with complications and 30-day and 1-year mortality were assessed.ResultsAmong them (mean age 67.1 ± 13.8 years, 73.9% male), only 325 (20.9%) reached the therapeutic range. Mean TTR was 12.5 ± 20.2%. An early invasive strategy predominated: 85.5% underwent coronary angiography, approximately 89% of them within 24 hours (mean time to angiography 14.4 ± 10.1 hours). Therapeutic-range attainment was not associated with mortality at 30 days (4.6% vs 4.0%, p=0.614) or 1 year (8.6% vs 9.3%, p=0.710), even after multivariable adjustment (adjusted OR 1.30, 95% CI 0.70-2.40 and 0.98, 95% CI 0.62-1.55, respectively). It was also not associated with in-hospital complications, including re-infarction, stroke, stent thrombosis, or bleeding.ConclusionsTherapeutic aPTT was achieved infrequently, and neither therapeutic-range attainment nor TTR was associated with clinical outcomes. These findings suggest that, using a contemporary approach to NSTEMI with a short time to angiography in the great majority of cases, TTR does not represent an optimal marker of anticoagulation quality, warranting evaluation of alternative strategies. Given the low event rate, confirmation in larger, adequately powered studies is required.

Central post-stroke pain (CPSP) is a refractory complication that occurs after stroke and is classified as central neuropathic pain. Its pathophysiological mechanisms remain unclear and effective pharmacological treatments are limited. Previously, we demonstrated that hypothalamic orexin expression is reduced in a bilateral carotid artery occlusion (BCAO) mouse model of CPSP. Here, we investigated whether impairment of orexinergic signalling contributes to the pathophysiology of CPSP and whether chemogenetic activation of lateral hypothalamic (LH) orexin neurons alleviates mechanical hypersensitivity after cerebral ischaemia.

Mice were subjected to BCAO for 30 min. The von Frey test assessed mechanical hypersensitivity. To specifically activate orexin-expressing LH neurons, we bilaterally injected Flp-dependent adeno-associated viruses expressing excitatory DREADD hM3Dq into the LH of orexin-Flp mice.

BCAO mice showed significantly increased withdrawal responses to mechanical stimulation on Day 3 after a stroke. Hypothalamic prepro-orexin mRNA expression was significantly decreased in BCAO mice. Cleaved caspase-3-positive cells and glial activation were observed in the hypothalamus, including the LH. Chemogenetic activation of orexin neurons significantly attenuated BCAO-induced mechanical hypersensitivity in heterozygous Orexin-Flp mice but not in homozygous Orexin-Flp mice. The antinociceptive effect was inhibited by pretreatment with SB334867, an orexin receptor 1 antagonist.

These findings suggest that impaired hypothalamic orexinergic signalling may contribute to the pathophysiology of CPSP and that modulation of orexinergic signalling may represent a potential therapeutic strategy for post-stroke pain.

Central post-stroke pain (CPSP) lacks effective therapies, and its underlying mechanisms remain poorly understood. Using a mouse model of BCAO, we found reduced hypothalamic prepro-orexin expression together with neuroinflammatory and apoptotic changes in the hypothalamus. Chemogenetic activation of lateral hypothalamic orexin neurons attenuated mechanical hypersensitivity, at least in part through orexin receptor 1 signalling. These findings suggest that impaired hypothalamic orexinergic signalling contributes to the pathophysiology of CPSP and identify the orexinergic system as a potential therapeutic target for post-stroke pain.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by "copper avidity", which easily leads to the dysregulation of copper ion homeostasis. It is possible to develop targeted nanodrugs that selectively kill cancer cells via cuproptosis. However, the dense stroma of PDAC acts as an airtight wall, which not only limits the penetration and distribution of therapeutic agents but also promotes immunosuppressive mechanisms via its hypoxia-promoting effects, often leading to treatment failure. Thus, we developed a near-infrared (NIR)-responsive semiconductor polymer-metal‒organic framework (MOF) nanoreactor (SPNMCH) that was loaded with copper sulfide nanoclusters (CuS_x NCs) and hyaluronidase (HAase). This biomimetic semiconductor "bomb" extensively demolishes the wall (by highly activating HAase) and precisely eliminates tumor cells (through its active copper uptake to induce cuproptosis). Simultaneously, the synergistic effects of increased oxygen delivery and cuproptosis elicit robust antitumor immune responses to inhibit tumor progression and distant metastasis, and strong immune memory effects as observed in four mouse cancer models. Additionally, SPNMCH can be combined with anti-programmed death receptor 1 (PD-1) antibodies to further promote T cell-mediated antitumor immunity. This study reveals a promising strategy for establishing a "hot" tumor immune niche in PDAC to promote the response to immunotherapy.

To evaluate cumulative radiation exposure associated with contemporary diagnostic pathways in patients with suspected chronic coronary syndromes (CCS), and to assess the impact of first-line imaging strategies, downstream testing, geographic variability, and adoption of guideline-recommendations on radiation burden.

This sub-analysis of the prospective, multicentre EURECA Imaging registry included 2058 patients (out of 2306 with available radiation data) undergoing at least one ionizing imaging test across 24 countries. Effective dose (ED) was calculated for each modality and cumulatively across diagnostic pathways. Median cumulative ED differed significantly according to initial testing strategy (p < 0.001). Single-photon emission computed tomography (SPECT)-first and computed tomography coronary angiography (CTCA)-first approaches were associated with a significantly lower radiation exposure (median ED 6.68 mSv, IQR 5.12-9.05 and 6.86 mSv, IQR 5.32-10.64, respectively), than an invasive coronary angiography (ICA)-first strategy (12.60 mSv, IQR 3.86-35.68). Marked inter-regional variability was observed across all modalities, with the highest doses generally reported in Eastern and Southern European countries. Guideline-adopting diagnostic pathways were associated with significantly lower cumulative ED in several regions. At multivariable analysis, hypertension, obesity, former smoking, and family history of coronary artery disease were independently associated with higher radiation exposure, while female sex, non-anginal symptoms, and guideline adoption predicted lower ED (all p < 0.01).

Cumulative radiation exposure in CCS varies substantially according to diagnostic strategy and practice patterns. Non-invasive, guideline-adopting pathways are associated with lower radiation burden, whereas ICA-first approaches lead to higher exposure. Optimizing test selection and promoting guidelines adoption may improve radiation safety in cardiovascular imaging.

Pre-eclampsia is a pregnancy complication that involves the development of high blood pressure in a pregnant woman and other features such as protein in the woman's urine, kidney or liver problems, or poorer growth for the baby. It can also have long-term health impacts for the mother after pregnancy. Pre-eclampsia typically occurs after 20 completed weeks of pregnancy (either mid-pregnancy known as 'early onset pre-eclampsia' or, more commonly, later in pregnancy, at or after 34 weeks, known as 'late onset' pre-eclampsia). Different blood pressure medications can be used to treat this condition, but not all women respond in the same way to the same medication. This is probably due to variables in the function of the maternal heart and blood vessels. Over the past 20 years, technological developments have meant it is now possible to measure important individual aspects of maternal cardiovascular function, using simple non-invasive tests. These tests can establish whether the mother's heart and circulatory system have any unusual features that may place her at higher risk of complications. They can also be used to monitor whether the mother's health and circulatory system is adapting in the right way to the pregnancy. For example, it is now possible to measure cardiac output (volume of blood pumped out by the heart) and vascular resistance (the physical resistance to the flow of blood), as well as the mother's blood pressure. It is also possible to monitor if and how changes in the above follow the patterns of change that are usually seen during pregnancy. Testing, and repeat testing as necessary, can identify individual measurements, or patterns of measurements, of concern and can identify whether the mother's heart and blood flow are adapting to the pregnancy in the typical and expected way. Studies in these areas have shown two distinct patterns of abnormal measurements of blood circulation and heart health in the pregnant woman that can occur with pre-eclampsia. Some changes and abnormalities can be detected before the symptoms of pre-eclampsia become obvious. Some features associated with pre-eclampsia can also be detected early in pregnancy or even before pregnancy. For example, we understand that some pregnant women who have a lower volume of blood being pumped out of their hearts per minute (low cardiac output), are more at risk of being affected by pre-eclampsia earlier in pregnancy, and more likely to have a baby with a low birth weight. Women that develop pre-eclampsia later in pregnancy typically have more circulating blood and babies of normal or larger size. The distinct measurable features of maternal heart health and blood flow can be used to identify those women at risk of developing pre-eclampsia at an early stage. Recognising the features of maternal heart health and the patterns of blood flow associated with pre-eclampsia provides an opportunity to individualise treatment plans for pregnant women, such as a personalised plan of monitoring and review, and using the most appropriate drugs that are tailored to address specific difficulties and likely to be most effective in restoring balance to the circulatory system of that individual. Early recognition, before the onset of symptoms, also allows timely reviews, and appropriate treatment to be started sooner. This, in turn, can lower the incidence of serious manifestations of pre-eclampsia for the mother, such as the development of seizures or a stroke. There is clear evidence that the management of pre-eclampsia can be improved by more detailed cardiovascular evaluation and tailored monitoring. The drugs that lower blood pressure work in different ways and the opportunity exists to target therapy to the underlying problem, however at the time of writing, many of the non-invasive tests and assessments able to identify women at risk of pre-eclampsia are typically only being used in a research setting. Routine clinical use of the available tests, and the establishment of clear care pathways and defined parameters for risk assessment based on those maternal heart and circulation test results, would allow targeted treatment and assist in preventing avoidable harm.