Vascular Ehlers-Danlos syndrome (vEDS), caused by likely pathogenic COL3A1 variants, carries a high risk of arterial dissection or rupture, intestinal perforation and uterine rupture, and a median survival near 51 years. It is often recognized only at a catastrophe, and its acute management is deliberately counter-intuitive. The therapeutic landscape changed in 2025 with the first randomized evidence for an angiotensin-receptor blocker. We provide a clinical, practice-oriented review for internists and the multidisciplinary team. As is appropriate for a rare disease, case-level evidence was considered alongside cohorts and trials. Suspicion is the rate-limiting step, and we set out speciality-specific red flags. Diagnosis requires molecular confirmation, with differentiation from other heritable arteriopathies. Genotype is a probabilistic predisposition, not a deterministic predictor: there is ascertainment bias, reduced penetrance and intrafamilial variability temper inference. Emergency care is harm-avoidant-catheter angiography, elective endoscopy and unnecessary surgery should be avoided, and endovascular and tissue-sparing techniques preferred. Pharmacological prevention rests on celiprolol, with randomized evidence now supporting irbesartan added to background celiprolol, and expert-centred consideration of angiotensin-receptor blockade when celiprolol is not tolerated. Surveillance should be individualized along the European Reference Network on Rare Multisystemic Vascular Diseases logic. Pregnancy, psychosocial care and cascade testing complete lifelong management. In vEDS, earlier recognition and the avoidance of iatrogenic harm-not new molecules-offer the largest near-term gains in survival and quality of life.

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerotic cardio-cerebrovascular disease. The role of impaired mitochondrial dynamics in the pathophysiological process of aging-related diseases is being actively researched. We discovered that targeting proteins related to mitochondrial dynamics, especially those involved in fission and fusion, may offer new treatment strategies for these diseases. Various approaches, including aerobic interval and treadmill training and the use of drugs such as the antidiabetic agents metformin and dapagliflozin, the antihypertensive agent irbesartan, and certain traditional Chinese medicine components, have shown potential in alleviating imbalances in mitochondrial dynamics in aging-related cardio-cerebrovascular diseases. In this review, we systematically summarize recent research on alterations in mitochondrial dynamics in age-related cardio-cerebral diseases and explore therapeutic strategies targeting these alterations, which may offer new directions for improving cardiac and brain health and guiding clinical practice.

Glaucoma is a neurodegenerative eye disease characterized by progressive loss of retinal ganglion cells (RGCs), resulting in irreversible vision loss. Previous work demonstrated that irbesartan, an angiotensin II type I receptor blocker, promotes RGC survival in rat retinal explants. This study extends these findings to ex vivo mouse explants, in vivo optic nerve crush model, and transcriptomic analysis to identify associated pathways. Retinal explants from C57BL/6 mice were cultured for 4 days with irbesartan (10 μmol/L), vehicle, or angiotensin II (2 μmol/L). RGC survival was assessed by βIII-tubulin and RNA-binding protein with multiple splicing (RBPMS) immunostaining; superoxide and mitochondrial density were measured using dihydroethidium and MitoTracker Red CMXRos. Mice received vehicle or irbesartan (10 μmol/L) eye drops for 7 days after optic nerve crush to assess RGC survival. Irbesartan enhanced RGC survival in explants (1.5-fold and 4-fold; P = 0.0138 and 0.000129) and in vivo (1.7-fold; P = 0.0045). Irbesartan reduced dihydroethidium intensity (P < 0.0072) and preserved mitochondrial labeling at day 2 (P = 0.02). RNA sequencing revealed differential expression of electron transport chain genes (eg, Cox4i2 and Ndufa12), with gene set enrichment analysis showing enrichment of proinflammatory pathways in vehicle-treated explants and neuronal/metabolic pathways with irbesartan. In conclusion, irbesartan reduces oxidative stress and modulates mitochondrial and inflammatory pathways, potentially supporting RGC survival, thus providing insights relevant to glaucoma and optic neuropathies involving RGC degeneration.

Historically, IgA nephropathy (IgAN) was managed using supportive care, with a suggested 6 months of immunosuppressive therapy considered for patients at high risk of progressive kidney function decline (proteinuria, >0.75-1 g/d) despite ≥90 days of optimized supportive care. The evolving treatment landscape includes agents that target immunologic aspects of IgAN or better preserve kidney function, or both. Recent approvals include Nefecon, sparsentan, iptacopan, atrasentan, and sibeprenlimab. Nefecon, a targeted-release formulation of budesonide, is the only US Food and Drug Administration and European Medicines Agency fully approved agent that is designed to target the primary source of IgAN: galactose-deficient IgA1 production in the gut mucosa. Phase 3 data showed that Nefecon slowed estimated glomerular filtration rate decline and decreased proteinuria versus placebo, with an acceptable safety profile. Sparsentan, a fully US Food and Drug Administration- and European Medicines Agency-approved dual endothelin A/angiotensin II receptor antagonist, affects the generic responses to IgAN-induced nephron loss, potentially including glomerular inflammation and fibrosis. Sparsentan demonstrated a significant reduction in proteinuria and estimated glomerular filtration rate decline compared with irbesartan. Iptacopan inhibits complement factor B and has received accelerated US Food and Drug Administration approval. Interim phase 3 study data have shown that iptacopan significantly reduces proteinuria when compared with placebo. The endothelin A receptor antagonist atrasentan and A proliferation binding ligand inhibitor sibeprenlimab have also received accelerated US Food and Drug Administration approval, based on interim phase 3 results showing significant proteinuria reduction versus placebo in patients with IgAN. This expanded clinical armamentarium offers clinicians and patients greater choice and improved disease control in IgAN management.

Granular activated carbon (GAC) filtration is increasingly used for quaternary treatment of municipal wastewater to remove organic micropollutants, in line with the revised EU Urban Wastewater Treatment Directive (Directive (EU) 2024/3019). This review compiles and synthesises available, peer-reviewed, and long-term pilot- and full-scale studies and, in contrast to previous reviews, particularly addresses breakthrough of Urban Wastewater Treatment Directive (UWWTD) relevant indicator compounds in relation to operational lifespan and regulatory compliance. Most studies were conducted at pilot scale, with considerable variation in empty bed contact time, filtration rate, and GAC type. Breakthrough of indicator compounds varied widely, but citalopram, metoprolol, benzotriazole, and methylbenzotriazole generally showed relatively late breakthrough, indicating potential for longer filter lifespan, whereas candesartan and irbesartan more often showed early breakthrough. The available data further indicate that the selection of indicator compounds strongly affects the operational lifespan over which compliance with the UWWTD may be maintained. However, the limited number of long-term full-scale studies and the large variability in pre-treatment, filter design, carbon type, and operating conditions prevent robust quantitative assessment of these relationships. The findings highlight the need for more large-scale, long-term studies using a systematic evaluation framework to support the effective implementation of GAC filtration for UWWTD compliance.

Because no information is available on the use of irbesartan during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Focal segmental glomerulosclerosis (FSGS) represents a heterogeneous clinicopathological entity characterized by podocyte injury, progressive glomerular scarring, and a high risk of progression to end-stage renal disease. Despite advances in understanding its pathophysiology, therapeutic options have remained limited, largely centered on supportive care and immunosuppression, with inconsistent efficacy and significant adverse effects. The recent approval of sparsentan, a dual endothelin type A and angiotensin II type 1 receptor antagonist, marks a significant advancement in the management of FSGS by targeting key hemodynamic and molecular pathways implicated in disease progression. This article provides a comprehensive overview of the pathogenesis of FSGS, emphasizing the central role of podocyte injury and maladaptive responses to mechanical stress. It further reviews current treatment strategies and examines the clinical evidence underpinning the approval of sparsentan, particularly findings from the DUPLEX trial. Although sparsentan did not demonstrate a statistically significant benefit in preserving estimated glomerular filtration rate, it achieved a clinically meaningful reduction in proteinuria compared with irbesartan. The safety profile was generally acceptable, with manageable adverse effects, including hyperkalemia and hypotension. While sparsentan introduces a novel, non-immunosuppressive therapeutic option, its long-term impact on renal outcomes remains to be fully established. Ongoing research will be critical to defining its role within combination regimens and optimizing patient selection in this complex disease spectrum.

Intervertebral disc degeneration (IDD) is a primary cause of chronic low back pain, yet the specific cell subpopulations and metabolic mechanisms driving its progression remain incompletely understood. We performed an integrative analysis of single-cell RNA sequencing (scRNA-seq) and transcriptomic sequencing using public datasets (GSE230809, GSE186542) to characterise cellular heterogeneity in IDD. To elucidate the underlying pathological mechanisms, we employed senescence scoring, transcriptional entropy assessment, pseudotime trajectory inference, and hierarchical weighted gene co-expression network analysis (hdWGCNA). Metabolic pathway activity was evaluated with scMetabolism, and potential therapeutics were screened using the POINT platform. We identified a key fibrochondrocyte subpopulation, FC3, which exhibits high transcriptional entropy and plays a central role in IDD. The FC3 cluster was further resolved into three functional states: fibrotic, proliferative, and metabolic. Pseudotime trajectory inference indicated that FC3 (proliferative) cells potentially represent a progenitor-like state, partitioning toward fibrotic and metabolic lineages. Notably, the FC3 (metabolic) state displayed the lowest senescence score and the highest activity in the tricarboxylic acid (TCA) cycle. Through hdWGCNA and cross-dataset validation, malate dehydrogenase 2 (MDH2) was established as a central hub gene linking TCA cycle activation to the FC3 (metabolic) phenotype. Functional enrichment confirmed MDH2's role in oxidative phosphorylation, fatty acid metabolism, and cellular senescence. Drug screening identified several candidate compounds, including Platycodin D, Irbesartan, and Ergothioneine, whose corresponding targets exhibited specifically enhanced activity within the FC3 (metabolic) subpopulation of degenerated tissues. Our study reveals that metabolic dysregulation in the FC3 fibrochondrocyte subpopulation, driven by aberrant MDH2-mediated TCA cycle activation, is a critical mechanism promoting IDD. These findings highlight the therapeutic targeting value of the FC3 metabolic state and provide specific candidate compounds for the subsequent development of interventions against IDD.

Pharmaceutical transformation products (TPs) can pose greater environmental risks than parent compounds, yet their occurrence in surface waters remains inadequately characterized. This study employed retrospective analysis of non-target screening (NTS) data, literature mining, and molecular networking to characterize pharmaceutical TPs in the Pearl River Basin (PRB). Suspect screening against TP databases identified 74 TPs, while molecular networking revealed 62,387 feature pairs sharing common MS/MS fragments. Structural annotation suggested 51 TPs derived from 28 parent pharmaceuticals, including 26 previously unreported compounds. Hydroxylation, methylation, demethylation, and oxidation were the dominant transformation pathways, showing minimal sub-basin variation-indicating structural control over transformation processes. Predictive assessment revealed 65% of TPs exhibited enhanced mobility and 23% showed increased toxicity relative to parent compounds. Notably, the TP SR-49498 showed a significantly higher environmental risk quotient (RQ = 13.271) than its parent Irbesartan (RQ < 0.0001). Toxicological Priority Index (ToxPi) analysis prioritized 12 high-risk TPs. Overall, this study systematically characterized the occurrence and environmental risks of pharmaceutical TPs in the PRB, thereby advancing the understanding of their environmental fate and providing a scientific basis for future water pollution monitoring and risk management strategies.