Search Results (5)

Immunosenescence, defined as the progressive decline of immune function with age, is increasingly recognized as a determinant of morbidity in people living with HIV (PLWH) and in individuals with metabolic dysfunction. The coexistence of chronic viral infection and systemic metabolic alterations—including metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus—creates a pro-inflammatory state (“metaflammation”) that accelerates immune aging. This narrative review synthesizes current clinical, translational, and experimental evidence on the cellular, molecular, and metabolic mechanisms underlying immunosenescence in HIV-positive and HIV-negative populations with metabolic dysfunction. Key converging pathways include chronic inflammation, mitochondrial dysfunction, microbial translocation, and altered immunometabolic signaling, leading to features such as CD8⁺CD28⁻ T-cell expansion, reduced CD4/CD8 ratios, and impaired vaccine responses. Biomarkers such as iAge, IMM-AGE, and the triglyceride–glucose (TyG) index have emerged as promising tools to quantify immune aging beyond chronological measures. Understanding these interconnected mechanisms offers opportunities for targeted interventions—such as metabolic reprogramming, microbiota modulation, and geroscience-based strategies—aimed at preserving immune resilience and promoting healthy aging in high-risk populations. Full article

Background: Ibrutinib has been associated with an increased risk of cardiovascular adverse events (CVAEs), including atrial fibrillation (AF), hypertension (HTN), heart failure (HF), and ventricular arrhythmias (VAs). However, baseline predictors of CVAEs remain poorly characterized. In this study, we sought to identify baseline patient characteristics associated with the occurrence of ibrutinib-related CVAEs, with particular emphasis on parameters linked to the renin–angiotensin system. Methods: We conducted a prospective, single-center cohort study of consecutive patients treated with ibrutinib for B-cell malignancy, with systematic assessment of a predefined panel of potential predictors of CVAEs at baseline (NCT03678337). These predictors included demographic and clinical variables, 16 circulating biomarkers related to inflammation, fibrosis, and neurohormonal activation, as well as nine echocardiographic parameters. The primary objective was to evaluate the association between baseline patient characteristics and the occurrence of CVAEs from ibrutinib initiation through the end of follow-up. The CVAE endpoint was defined as a composite of atrial fibrillation, new or worsening hypertension, new or worsening heart failure, and ventricular arrhythmias. Statistical analyses were performed using the Wilcoxon–Mann–Whitney test or Fisher’s exact test, with a p-value < 0.05 considered statistically significant. Results: Among the 25 patients included, 7 experienced a total of 9 CVAEs over a median follow-up of 672 days. Elevated baseline plasma renin levels (>1336.10 pg/mL) were significantly associated with CVAEs occurrence (57% vs. 11%, p = 0.032). Higher baseline plasma aldosterone levels (>488.95 pg/mL) were also observed in patients who developed CVAEs, although this association did not reach statistical significance (p = 0.058). Conclusions: Baseline plasma renin level was univariably associated with CVAEs occurrence, while plasma aldosterone levels were higher among patients with CVAEs but did not reach statistical significance. These findings provide preliminary insights into the mechanisms underlying ibrutinib-related cardiovascular toxicity, suggesting a potential role for the renin–angiotensin–aldosterone system. Confirmation of this hypothesis, however, will require larger, dedicated studies. Full article

Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer (TC), accounting for 50% of total TC-related deaths. Although therapeutic approaches against TC have improved in recent years, the survival rate remains low, and severe adverse effects are commonly reported. However, unexplored alternatives based on natural compounds, such as lysicamine, an alkaloid found in plants with established cytotoxicity against breast and liver cancers, offer promise. Therefore, this study aimed to explore the antineoplastic effects of lysicamine in papillary TC (BCPAP) and ATC (HTH83 and KTC-2) cells. Lysicamine treatment reduced cell viability, motility, colony formation, and AKT activation while increasing the percentage of necrotic cells. The absence of caspase activity confirmed apoptosis-independent cell death. Necrostatin-1 (NEC-1)-mediated necrosome inhibition reduced lysicamine-induced necrosis in KTC-2, suggesting necroptosis induction via a reactive oxygen species (ROS)-independent mechanism. Additionally, in silico analysis predicted lysicamine target proteins, particularly those related to MAPK and TGF-β signaling. Our study demonstrated lysicamine’s potential as an antineoplastic compound in ATC cells with a proposed mechanism related to inhibiting AKT activation and inducing cell death. Full article

Background: Given the potential cardiovascular risks of androgen deprivation therapy (ADT), it is essential to identify patients who may be at an increased risk for coronary artery disease (CAD). Despite the recent ESC recommendations, there is no consensus on when to refer a patient to a cardiologist for further evaluation. Objective: To report on new diagnoses of CAD in patients with prostate cancer (PCa) requiring ADT who underwent a systematic cardio-onco evaluation with an assessment of their coronary status. Design, Setting, and Participants: This is a retrospective, monocentric study that included patients with PCa who had completed a cardio-onco evaluation with an assessment of their coronary status in the cardio-oncology department at the Western Cancer Institute, Nantes, between January 2019 and August 2022. Intervention: The baseline cardio-onco evaluation included a physical exam, transthoracic echography, and electrocardiogram, followed with a systematic evaluation of their coronary status. Outcome Measurements and Statistical Analysis: The primary objective was to determine the incidence of newly diagnosed CAD. The secondary objective was to evaluate the number of changes in cardiovascular treatment. Results and Limitations: Among the 34 patients who underwent cardio-onco evaluation, 7 (20.6%) were diagnosed with CAD, with a median time to diagnosis of 5 months. Most patients were asymptomatic, with one who experienced a myocardial infarction. Of the 27 patients without CAD, 44.4% underwent a therapeutic intervention by the cardiologist, with no cardiac deaths during follow-up. Overall, 55.9% of patients had a therapeutic intervention after the cardio-onco evaluation. Conclusions: The high incidence of newly diagnosed CAD in asymptomatic patients supports the need for screening for CAD in this population. Further research is needed to determine whether routine screening for CAD in patients receiving ADT would result in significant clinical benefits. Full article

It seemed unimaginable that the eye, denoting visuality and deemed accurate and reliable in accordance with Aristotelian theories in circulation during the Spanish Golden Age could be considered as anything other than a revered hallmark of guidance and intellect. Nevertheless, the literary phenomenon) of the picaresque emerged at the onset of the seventeenth century to defy the chivalric and pastoral fantasies that were masking the real anxieties faced by an era of decline. The picaresque genre brought warning that turning a blind eye to Spain’s already-waning fortunes could not last forever. Yet, by doing so, it lent favour to such blindness, underlining how the eye, both symbolically and substantially, actually evoked a sense of ill-fatedness and misfortune. This paper calls for an exploration of how an ominous utilisation of the eye is presented in the most canonical picaresque works: Lazarillo de Tormes and Mateo Alemán’s Guzmán de Alfarache. From the imperative role of the blind man in opening the eyes of the young protagonist, to the doomed interpolated cosplay of seeing and unseeing throughout Lazarillo’s trajectory, and from Guzmán’s receptivity to appearances and Alemán’s lending of visual lexicon to his picaro protagonist, one must ask: how and why does the bodily organ of the eye, through both notion and function, serve as a depiction of hardship and disaster within these picaresque texts, and how does it reflect the overarching societal views towards intellect and religion during this epoch of “ocularcentrism”? Full article