Introduction: Thoracic aortic aneurysm (TAA) is a life-threatening aortic disease often referred to as a “silent killer” because it progresses insidiously until reaching a critical stage, when aortic dissection or rupture may occur. The pathophysiology of TAA involves complex and dysregulated interactions between vascular smooth muscle cells (VSMCs) and the extracellular matrix (ECM), driven by genetic mutations, mechanical stress, inflammatory responses, and oxidative stress. However, the causal relationships and molecular links among these processes remain incompletely understood. Recently, microRNAs (miRNAs), a class of endogenous non-coding RNAs of approximately 22 nucleotides that regulate gene expression, have attracted increasing attention in TAA because of their remarkable stability, tissue specificity, and regulatory versatility, as well as their potential roles in both disease pathogenesis and biomarker development. Methods: A systematic literature search was conducted across Web of Science, PubMed, and other relevant databases using keywords related to TAA, microRNAs, VSMCs, ECM remodeling, pathogenesis, and biomarker. The retrieved studies were synthesized to examine miRNA-mediated regulation of VSMC dysfunction and ECM remodeling as a central mechanistic framework for TAA initiation and progression, while also integrating upstream drivers such as genetic alterations and mechanical stress, as well as modulatory processes including inflammation, oxidative stress, and endothelial-to-mesenchymal transition (EndMT). The translational potential of miRNAs as biomarkers and therapeutic targets, together with the key challenges to their clinical application, was also evaluated. Results: Current evidence indicates that miRNAs act as critical molecular regulators linking upstream pathogenic drivers, including genetic abnormalities and mechanical stress, to key downstream processes such as VSMC dysfunction, ECM remodeling, inflammation, oxidative stress, and EndMT. These interconnected mechanisms do not operate independently but rather interact and reinforce one another, thereby promoting aneurysm initiation and progression. In addition, a growing body of evidence suggests that TAA-related miRNAs may serve as promising biomarkers for early diagnosis and prognostic assessment, while also representing potential therapeutic targets. Conclusions: This review highlights the multifaceted roles of miRNAs in TAA and supports their value as an integrative framework for understanding disease pathogenesis. Although miRNAs show considerable promise as biomarkers and therapeutic targets, their clinical translation remains limited by heterogeneity, lack of standardization, and insufficient large-scale validation. Future efforts should focus on multicenter validation and integration with imaging and clinical data to advance the use of miRNAs in precision diagnosis and management of TAA.

Hypothesis/Introduction The renin-angiotensin system plays a central role in renal ischemia-reperfusion injury (IRI). We evaluated the effects of angiotensin-converting enzyme inhibitors (ACEIs) and AT1 receptor blockers (ARBs) in preclinical renal IRI models using multilevel and network meta-analyses (PROSPERO: CRD42024599859). Materials and Methods Database searches identified 55 studies. Serum creatinine data were pooled using three-level random-effects models (96 comparisons, n = 1233 animals). Publication bias was assessed using Egger and 1/√n methods. Drugs were ranked via P-scores. Results ACEIs/ARBs significantly reduced creatinine (standardized mean difference: −1.74; 95% CI: −2.22 to −1.26; p < 0.0001) with high heterogeneity. Egger's test showed asymmetry ( p < 0.0001), but 1/√n-based testing did not ( p = 0.160), suggesting mathematical artifact rather than publication bias. Multivariable meta-regression identified drug identity, dose, and route as key effect modifiers. Network analysis ranked azilsartan and telmisartan highest, though evidence remains limited (no direct comparisons, n = 2 for azilsartan). Secondary outcomes confirmed renal protection. Conclusions ACEIs/ARBs effectively reduce renal IRI in animals, with azilsartan and telmisartan ranking favorably despite limited evidence. High-dose intravenous administration enhances efficacy. Most studies used pre-ischemia protocols relevant only to transplantation. Post-injury models with comorbid animals of both sexes and direct drug comparisons are needed for clinical translation.

Aims: Diabetic cardiomyopathy (DCM) is a major complication of diabetes mellitus (DM) leading to increased morbidity and mortality. Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a central role in DCM pathogenesis. Data Synthesis: This narrative review was conducted through a comprehensive literature search of major scientific databases, including PubMed, Scopus, and Web of Science, using keywords related to oxidative stress, inflammation, and diabetic cardiomyopathy. Peer-reviewed experimental and translational studies were critically analyzed and synthesized to elucidate key molecular mechanisms. Conclusions: This review highlights the molecular interplay between oxidative stress and inflammatory pathways—including Nrf2, NF-κB, and Sirt1 signaling—in promoting myocardial fibrosis, apoptosis, and dysfunction. Furthermore, therapeutic strategies targeting oxidative stress and inflammation, such as natural antioxidants and Nrf2 activators, show promise in mitigating DCM progression. Understanding these mechanisms provides new insights into potential interventions to prevent and treat diabetic heart disease.

Introduction To further clarify the association between angiotensin receptor blocker therapy and post-stroke seizures, we analysed a database of patients with acute stroke. Methods This single-centre, retrospective observational study included patients with acute stroke admitted to our hospital between 1 January 2019 and 31 December 2023. Patients were allocated into two groups based on whether they received angiotensin receptor blocker therapy. The primary outcome was the incidence of any seizure in the two groups. Predictors of seizure occurrence were assessed in univariable and multivariable logistic regression models. Results A total of 2589 patients were enrolled; the mean age was 72 years (SD 13.2), and the majority were female (n = 1306, 50.4%). The median follow-up duration was 18 months (IQR 3–31). A total of 243 patients experienced at least one seizure, including acute symptomatic seizures only (n = 101), post-stroke epilepsy (n = 92), or both (n = 50). The differences in seizure incidence were significant across all three groups ( P < 0.05), and angiotensin receptor blocker therapy remained a significant factor in the multivariable logistic regression model ( P < 0.001). Conclusions Based on our results, angiotensin receptor blocker therapy is independently associated with a lower incidence of both acute symptomatic seizures and post-stroke epilepsy.

Background Cardiorenal syndrome (CRS) has evolved from a hemodynamic concept to a complex metabolic interplay, culminating in the 2023 definition of Cardiovascular-Kidney-Metabolic (CKM) syndrome. We analyzed the field's intellectual trajectory to guide future research. Methods We examined the 100 most-cited CRS articles (2003–2025) from the Web of Science. Using VOSviewer and CiteSpace, we mapped publication trends, collaborative networks, and keyword evolution to trace the shift from organ-centric to metabolic perspectives. Results Analysis reveals a bimodal trend: an initial peak driven by consensus definitions, followed by a recent wave focusing on metabolic integration. The United States and Italy were dominant contributors. Keyword analysis highlights a transition from hemodynamic terms to molecular mechanisms and metabolic risk factors (e.g., SGLT2 inhibitors), mirroring the conceptual expansion toward CKM. Conclusion High-impact research has shifted from phenomenological classification to mechanistic exploration of metabolic pathways. This evolution necessitates interdisciplinary collaboration and integrated therapeutic strategies targeting metabolic drivers, kidney injury, and cardiovascular remodeling to improve patient outcomes.

Background Copper metabolism dysregulation contributes to mitochondrial damage in diabetic retinopathy (DR). This study investigated whether dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, alleviates DR by regulating copper homeostasis. Methods Clinical serum analysis, high glucose-exposed ARPE-19 cells, and diabetic rat models were used. Measurements included copper/ceruloplasmin levels, oxidative stress, mitochondrial function, and mitophagy markers. Results Clinical test results show that the levels of ceruloplasmin and copper in the serum of patients with proliferative diabetic retinopathy (PDR) are significantly higher than those of diabetic patients. High glucose induced copper/ceruloplasmin accumulation, downregulated ATP7B/SOD1/COX11/ATP7A/CCS, upregulated SCO1/DMT1, and impaired mitochondrial function in retinal pigment epithelial (RPE) cells. Dulaglutide reversed these effects, reducing oxidative stress and inflammation while restoring mitochondrial integrity. Crucially, it activated PINK1/Parkin-mediated mitophagy. The protective effects were abolished by CuSO 4 , confirming copper homeostasis as central to its mechanism. In diabetic rats, dulaglutide corrected retinal copper metabolism abnormalities, ameliorated histopathological damage, and enhanced mitophagy, thereby preserving mitochondrial function and alleviating diabetic retinopathy. Conclusion Dulaglutide ameliorates DR by correcting copper dysregulation and promoting mitophagy, highlighting copper homeostasis as a potential therapeutic target.

Childhood depression has become an increasingly significant issue in global public health. While traditional medication and counseling are commonly used, non-pharmacological interventions are gaining popularity due to the limitations of conventional approaches. This research explores the potential benefits of exercise, music therapy, and dance therapy in treating childhood depression, with a particular focus on the renin-angiotensin system (RAS) and its role in mood regulation. The RAS, which regulates blood pressure and fluid balance, is linked to various mood disorders, including depression. Regular physical activity can help reduce stress levels, enhance serotonin balance, and regulate the norepinephrine-angiotensin system. Dance therapy, through repetitive movements, fosters personal expression and reduces communication barriers. Studies indicate that structured exercise can significantly alleviate depression, and group-based music and dance interventions are especially beneficial for socially withdrawn children. Future efforts should focus on enhancing multidisciplinary collaboration, integrating these therapies into educational programs, and developing more targeted interventions. Schools have a key role in ensuring that these interventions are accessible, feasible, and effectively implemented, helping create a comprehensive support system for children's physical and mental well-being.

Objective The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a critical unsolved clinical problem. Mitochondrial homeostasis and macrophage function are pivotal in this process. This study aimed to investigate whether glycine amidinotransferase (GATM), a key enzyme in creatine biosynthesis, mediates mitophagy and macrophage function to participate in AKI-to-CKD progression. Methods A renal ischemia-reperfusion (I/R) model was established in myeloid-specific GATM knockout (LysM-cre + /GATM fl/fl ) and control (LysM-cre + /GATM +/+ ) mice ( n = 3 per group, 3 independent replicates). Renal pathological injury and fibrosis were evaluated by hematoxylin-eosin (HE) and Masson staining. Serum creatinine (Cr), blood urea nitrogen (BUN), and renal biomarkers (Kim-1, NGAL, creatine, IL-1β, TNF-α) were quantified via ELISA. Gene and protein expressions of GATM, Collagen I, α-SMA, and mitophagy-related molecules were assessed by RT-qPCR and immunohistochemistry/western blot. Macrophage polarization, mitochondrial ROS levels, and efferocytosis efficiency were analyzed by flow cytometry. In vitro, bone marrow-derived macrophages (BMDMs) were differentiated with macrophage colony-stimulating factor (m-CSF), and polymorphonuclear neutrophils (PMNs) were induced to apoptosis by serum-free starvation. Functional rescue experiments were performed using ALDH2 overexpression plasmids. Statistical analyses were conducted with t-test and one-way ANOVA. Results GATM deficiency significantly exacerbated the pathological damage induced by AKI and promoted the AKI-to-CKD progression, as evidenced by elevated serum creatinine and blood urea nitrogen levels, along with increased expression of Kim-1, NGAL, and fibrotic markers (Collagen I, α-SMA). The absence of GATM led to a reduction in creatine levels within BMDMs, downregulation of ALDH2 expression, inhibition of mitophagy, and an elevation of ROS in mitochondria. Concurrently, there was an enhanced polarization of BMDMs towards the M1 phenotype, accompanied by a diminished efferocytic capacity. Notably, in vitro overexpression of ALDH2 partially revived mitophagy activity, reset the polarization balance of BMDMs, and rejuvenated their efferocytic function. Conclusion Data suggest that GATM may regulate ALDH2-linked mitophagy via creatine, influencing macrophage polarization and efferocytosis during AKI-to-CKD transition. Targeting the GATM-ALDH2 pathway represents a promising novel therapeutic strategy for mitigating CKD development after acute kidney injury.

Introduction Heart failure (HF) patients are prone to postoperative hemodynamic instability after cardiac surgery, possibly due to upregulated renin-angiotensin-aldosterone system (RAAS) activity. We evaluated perioperative RAAS activity in control and HF patients and its impact on acute kidney injury (AKI) incidence. Materials and Methods Pre-specified analysis of a prospective observational cohort study (VASOR). Plasma renin, angiotensinogen and aldosterone were measured perioperatively in 18 control and 18 HF patients. Results RAAS blocker use was identical in both groups. HF patients displayed a diminished preoperative renal function. AKI occurred in 1 control and 8 HF patients. Preoperatively, HF patients exhibited 5-fold higher renin and aldosterone levels, identical aldosterone/renin ratios, and modestly lower angiotensinogen levels than controls. During surgery, renin rose 10-fold higher in HF patients. Aldosterone increased proportionally, but was blunted when normalized for renin (aldosterone/renin ratio). This was not due to angiotensinogen depletion. Postoperatively, angiotensinogen increased 50% in both groups, allowing aldosterone to increase, despite a modest postoperative renin decline. Preoperative renin levels and the surgery-induced renin rise predicted postoperative AKI. Conclusions HF patients exhibit dysregulated RAAS responses to surgery may reflect impaired angiotensin I-angiotensin II conversion. Elevated renin signals RAAS dysregulation, identifying patients who might benefit from angiotensin II infusion. The Netherlands Trial Register (NTR5647); http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5647 .