Chronic inflammation is a pathological mechanism of central importance that underpins a wide range of diseases, including neurodegenerative, cardiovascular, respiratory, gastrointestinal, and dermatological disorders. Ginkgo biloba extract (GBE), a standardized formulation derived from Ginkgo biloba leaves, has attracted growing attention due to its anti-inflammatory, antioxidant, and neuroprotective properties. This review comprehensively summarizes the current preclinical and clinical evidence regarding the therapeutic potential of GBE and its active constituents in inflammation-related diseases. GBE has been shown to attenuate pro-inflammatory cytokine production, suppress nuclear factor kappa B (NF-κB) activation, restore redox homeostasis, and modulate disease-relevant pathways in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, atherosclerosis, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, inflammatory skin conditions and rheumatoid arthritis. While these findings highlight the promising multi-targeted anti-inflammatory actions of GBE, limitations remain regarding the identification of specific active compounds, standardization of formulations, and the availability of robust clinical evidence. Further research is warranted to clarify the mechanisms of action and optimize delivery of GBE, and to validate the efficacy and safety of GBE in large-scale clinical trials.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as pivotal agents in the treatment of type 2 diabetes (T2D) and obesity, with well-established metabolic and cardiovascular benefits that translate into improvement in quality of life and life expectancy. While a potential benefit may also be hypothesized in patients with metabolic disorders and malignancy, robust clinical evidence is still lacking. In recent years, attention has turned to their potential impact on cancer risk, although current evidence remains limited and, in some cases, conflicting. Several biological pathways, such as improvements in insulin sensitivity, reductions in chronic inflammation, modulation of cellular signaling, and changes in the tumor microenvironment, have been proposed as possible mechanisms through which GLP-1RAs might influence cancer development or progression. However, available data derive from preclinical or observational studies, and high-quality prospective clinical evidence is still lacking. While some reports suggest possible protective associations in specific cancer types, others raise concerns about potential risks, particularly in hormonally sensitive or receptor-expressing tissues. This position paper synthesizes available data on the oncologic safety and potential antitumor effects of GLP-1RAs, highlights key knowledge gaps, and discusses clinical implications, underscoring the need for further research to clarify their role in cancer prevention and treatment.

The Osaka Prognostic Score (OPS), which is based on C‑reactive protein (CRP), total lymphocyte count (TLC), and albumin (ALB), has been reported to have prognostic value in several types of cancer. Recent studies have revealed a relationship between the OPS and cardiovascular diseases. The aim of this study was to evaluate the relationship between the OPS and paroxysmal atrial fibrillation (AF), a significant rhythm disorder.

A total of 941 individuals, including 198 patients with a history of AF and 743 patients without AF as the control group, were included in the study. These groups were compared in terms of demographic characteristics and laboratory findings.

Univariable and multivariable binary logistic regression analyses revealed an independent relationship between the OPS and AF (odds ratio [OR]: 3.37, p < 0.001). In receiver operating characteristic (ROC) curve analysis, OPS above a cut-off level of 0.5 was associated with the presence of AF, with a sensitivity of 55.6% and a specificity of 77.4% (area under the ROC curve [AUC]: 0.682, p < 0.001).

This study found a relationship between the OPS and paroxysmal AF attacks. The OPS may provide additional information for the clinical evaluation of patients with paroxysmal AF in daily practice.

Daily apparel could enable continuous, noninvasive monitoring of cardiopulmonary health for the early detection and treatment of cardiopulmonary diseases, the leading causes of death and disability worldwide. Here we develop an all-fiber wireless auscultation system seamlessly integrated into garments. An ~150-μm-diameter fiber contact microphone is sewn, knitted or woven into clothing to capture deep-body acoustic signals while overcoming acoustic impedance mismatch and electromagnetic noise. An ~500-μm knitted fiber computer enables real-time signal processing and Bluetooth transmission to a mobile device. A clinical study in 10 patients with heart failure and 20 neonates demonstrated cardiopulmonary sound capture, including qualitative examples of pathological acoustic features such as cardiac murmurs, S3 gallops and crackles. Comparative validation against a digital stethoscope confirms the garment's ability to suppress environmental noise for high-fidelity cardiopulmonary sound capture. In addition, the fiber integrated within the garment array enables spatial sound mapping of cardiac and pulmonary abnormalities for localized diagnostics.

Gene-regulatory networks (GRNs) offer a mechanistic framework for dissecting the complex molecular and genetic architecture of coronary artery disease and for identifying new therapeutic opportunities. Here, we present a GRN-driven drug-repurposing strategy that integrates transcriptional signatures induced by silencing key drivers of the human arterial wall foam cell regulator GRN 42 with drug-induced gene expression profiles from the NIH LINCS program. In vitro screening of top candidate compounds validates the computational predictions, identifying candidate foam cell modulators and showing that auranofin, an FDA-approved gold salt used to treat rheumatoid arthritis, effectively reduces foam cell formation. In vivo, auranofin attenuates atherosclerosis and inflammation in both male mice and rabbits. Clinically, auranofin was associated with reduced cardiovascular risk in a retrospective cohort of patients with rheumatoid arthritis. Together, these findings show that a GRN-based drug-repurposing framework, coupled with preclinical and clinical validation, can uncover new therapeutic applications for existing drugs, including auranofin, in coronary artery disease.

Overactivation of Notch signaling in liver sinusoidal endothelial cells (LSECs) is an established driver of hepatic fibrosis, yet its precise upstream regulators and downstream effectors remain poorly defined, limiting therapeutic translation. Here, we demonstrate that FBXW7, the primary E3 ubiquitin ligase responsible for NOTCH1 degradation, serves as a critical suppressor of liver fibrosis. Using endothelial-specific Fbxw7 knockout mice subjected to three distinct fibrosis models, we show that FBXW7 loss exacerbates liver fibrosis, promotes LSEC capillarization, and enhances hepatic stellate cell activation. Transcriptomic analysis identified Sema3g as the top upregulated gene in FBXW7‑deficient LSECs, and conditioned medium from these cells stimulated HSC activation through SEMA3G‑dependent paracrine signaling. Moreover, nanoparticle-mediated delivery of Sema3g-targeting siRNA specifically to LSECs substantially ameliorated injury-induced liver fibrosis in Fbxw7 knockout mice. Mechanistically, FBXW7 loss stabilizes NOTCH1, leading to enhanced Sema3g transcription. Consistent with these findings, human cirrhotic samples and murine fibrotic livers exhibit reduced FBXW7 expression alongside elevated active NOTCH1 and SEMA3G in LSECs. Collectively, our results demonstrate that FBXW7 mitigates liver fibrosis by degrading NOTCH1 to transcriptionally silence SEMA3G, and suggest that targeting the FBXW7/NOTCH1/SEMA3G axis represents a promising therapeutic strategy for fibrotic liver disease.

Ticagrelor, a commonly used antiplatelet medication, has been found to exhibit considerable inter-individual pharmacodynamic variability. Recent studies have revealed a close relationship between pharmacokinetics and pharmacodynamics, both of which can be influenced by gut microbiota. In this study, we explored whether the pharmacokinetics of ticagrelor is mediated by intestinal flora. We enrolled 22 healthy participants to assess the clinical pharmacokinetic profiles of ticagrelor and its metabolite AR-C124910XX after a single oral dose of ticagrelor. The fecal microbial compositions of individuals who exhibited distinct pharmacokinetic parameters were analyzed using 16S rRNA gene sequencing. Additionally, we conducted experiments involving the co-incubation of ticagrelor with fecal bacteria and a systematic exploration of the pharmacokinetics of ticagrelor in pseudo-germ-free (PGF) rats to illustrate the role of gut microbiota in ticagrelor metabolism, both in vitro and in vivo. Our findings revealed a three-fold difference in the bioavailability of ticagrelor among individuals. However, no difference was found in the composition of gut microbiota among individuals with different pharmacokinetic parameters. Quantitative analysis showed that gut microbiota cannot directly metabolize ticagrelor. Furthermore, there were no significant differences in AUC(0-48), AUC(0-∞), and Cmax between ticagrelor and AR-C124910XX in PGF rats compared to normal control, either by single intragastric or intravenous administration. In conclusion, these findings suggest that gut microbiota has no impact on the pharmacokinetics of ticagrelor.

[This corrects the article DOI: 10.3389/fimmu.2026.1818835.].

Atherosclerosis (AS) poses major challenges for precise diagnosis and targeted therapy due to its complex inflammatory and oxidative plaque microenvironment. This review begins by dissecting the cellular and molecular hallmarks of AS progression, from endothelial dysfunction to plaque rupture, identifying key targets including adhesion molecules, scavenger receptors, and immune costimulatory pathways that can be exploited for nanotheranostic intervention. Rare-earth nanoparticles (RENPs) offer a versatile platform that integrates multimodal imaging with therapeutic functions. We highlight the strategic design of RENPs, including core-shell engineering, surface functionalization, and doping strategies, to enhance NIR-II luminescence, lifetime multiplexing, and X-ray-activated persistent luminescence for high-resolution vascular imaging and fluorescence-guided surgery. Their intrinsic enzyme-mimetic activities, particularly the cerium-based nanozymes that scavenge reactive oxidative species, are examined as a key therapeutic mechanism targeting oxidative stress within plaques. A critical discussion of biocompatibility analyzes the element- and form-dependent toxicity profiles, emphasizing the divergent effects between therapeutic nanomaterials and potentially harmful rare-earth ions. These insights underscore the necessity of rigorous safety evaluations alongside functional development. Finally, we outline future directions and challenges in the clinical translation of RENP-based theranostic strategies, emphasizing the need for optimized targeting, biosafety, and multifunctional integration to achieve the precise diagnosis and effective treatment of atherosclerotic cardiovascular diseases.

Growth differentiation factor 15 (GDF15) is a stress responsive cytokine belonging to the transforming growth factor-β (TGF-β) superfamily, serving as a sentinel of metabolic integrity. Its expression is induced by multiple convergent stress pathways, including the integrated stress response (ISR), endoplasmic reticulum (ER) stress, oxidative stress, inflammation, and hypoxia. GDF15 is secreted by a wide range of organs, such as adipose tissue, skeletal muscle, liver, heart, kidney, immune cells, and the central nervous system, with the relative contribution of each tissue varying across different physiological and pathological states. Through the hindbrain GFRAL-RET axis, GDF15 suppresses appetite and regulates energy balance, while also exerting peripheral effects on mitochondrial function, insulin sensitivity, and inflammatory responses. Transient GDF15 elevation in response to acute stressors supports adaptive metabolic resilience and tissue protection. In contrast, chronic and sustained elevation signals progressive metabolic dysfunction, organ impairment, and poor prognosis in conditions including obesity, metabolic dysfunction associated steatotic liver disease (MASLD), diabetes, and cardiovascular disease. Importantly, the biological impact of GDF15 is modified by factors such as age and metabolic context, which may shift the balance between adaptive and maladaptive outcomes and account for much of the predictive signal in clinical studies. Although GDF15 holds promise as a prognostic biomarker and a therapeutic target, its clinical translation is hindered by two major challenges: its dual protective and pathological roles, and an incomplete understanding of non-GFRAL signaling pathways. This narrative review summarizes the regulatory networks, tissue sources, and context-dependent functions of GDF15, with an emphasis on its roles in cardiometabolic homeostasis and the potential for future precision therapeutic strategies. We present the sentinel model as a working hypothesis that generates testable predictions, rather than as a proven biological mechanism. The acute-adaptive versus chronic-maladaptive distinction, while conceptually useful, requires validation through measurable parameters including concentration thresholds, temporal dynamics, and tissue specific contributions.