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Eur J Epidemiol. 2025 Jul 2. doi: 10.1007/s10654-025-01258-1. Online ahead of print.

ABSTRACT

The TransplantLines Biobank and Cohort Study (NCT03272841) is an ongoing prospective study conducted at the University Medical Centre Groningen, The Netherlands. TransplantLines aims to identify risk factors and biomarkers associated with health problems following solid organ transplantation and donation. Additionally, the study seeks to develop new interventions to reduce symptom burden and improve long-term outcomes, including health-related quality of life, cardiovascular complications, graft failure, and mortality. It includes recipients of (combined) heart, liver, lung, kidney, pancreas, and small bowel transplants, as well as living liver and kidney donors, and deceased (multi-)organ donors. The biobank contains a wide range of biomaterials including whole blood, serum, EDTA-plasma, buffy coat, 24-h urine samples, faeces, hair, nails, and tissues. Data collection includes physical and cognitive assessments, extensive laboratory analysis, metagenomic sequencing, and questionnaires. TransplantLines, initiated in 2015, consists of 5143 participants as of October 2024, among 2312 (45%) females. The mean age was 50 (± 16) years at transplantation, 55 (± 11) years at living donation and 56 (± 15) years at deceased donation. Both cross-sectional and longitudinal biomaterials and data are included. For recipients, longitudinal biomaterials and data were collected at: pre-transplantation, at transplantation, and at 3, 6, 12, 24, and 60 months post-transplantation. For living donors, data were collected at pre-donation, donation, 3 months post-donation, and/or 5 or 10 years post-donation.

PMID:40601244 | DOI:10.1007/s10654-025-01258-1

Can J Anaesth. 2025 Jul 2. doi: 10.1007/s12630-025-02979-3. Online ahead of print.

ABSTRACT

PURPOSE: Cardiac donation after death determination by circulatory criteria (DCC) can be performed using either 1) direct procurement and perfusion of ex situ organs or 2) normothermic regional perfusion (NRP). Nevertheless, there are concerns regarding the acceptability and ethics of these procedures, particularly NRP in which the blood supply to the brain is surgically interrupted and circulation in the thorax and abdomen is restored prior to heart retrieval. We aimed to understand the perspectives on cardiac donation following DCC of Canadian clinicians who are involved in donation and transplantation.

METHODS: We performed a qualitative descriptive study of 75 clinicians to better understand the perspectives of physicians on cardiac DCC. We purposively sampled clinicians who care for organ donors (N = 51) and those who care for transplant recipients (N = 24) in Canada. We performed thematic analysis to generate themes describing participants' perspectives about cardiac DCC and its implementation in Canada.

RESULTS: We found that the broad support and interest to implement cardiac DCC among the cohort of clinicians interviewed was tempered by their anticipation that other clinicians, donor families, and the public would be less supportive. Donor clinicians were particularly concerned about potential erosion in public trust in the organ donation system as a whole. Participants identified opportunities to address anticipated challenges, including strategies for education and communication around cardiac DCC, staged/gradual introduction of cardiac DCC, and the option for stakeholders (clinicians, donor families, potential transplant recipients) to opt out of participation in cardiac DCC.

CONCLUSIONS: In this qualitative study of clinicians involved in organ donation or transplantation across Canada, we found broad support for cardiac DCC. Nevertheless, we observed several challenges with the implementation of cardiac DCC, particularly concerns of nonsupport by other stakeholders. Participants also identified opportunities to address anticipated barriers.

PMID:40601238 | DOI:10.1007/s12630-025-02979-3

Ann Intensive Care. 2025 Jul 2;15(1):88. doi: 10.1186/s13613-025-01508-1.

ABSTRACT

BACKGROUND: Post-cardiac arrest (CA) care guidelines (GLs) have been introduced in 2010 and periodically updated every 5 years since then (in 2015 and 2021). However, the impact of these GLs on patients' outcome remains underexplored. The aim of this study was to comprehensively evaluate and compare the impact of implementation of three consecutive post-CA GLs over 14 years, on patients' survival and neurological recovery.

METHODS: This retrospective cohort study included adult patients resuscitated from CA and admitted to the intensive care unit (ICU) between 2011 and 2024. Patients were stratified into three cohorts based on the GL in use (GL2010, GL2015, and GL2024). Adherence to GL recommendations was assessed across seven macro-areas: coronary angiography, haemodynamic, ventilation, temperature control, general ICU management, multimodal neuroprognostication, and seizure control. Predictors of survival and favourable neurological outcome at ICU discharge were evaluated using multivariate logistic regression with LASSO selection. Outcome up to 6 months was also evaluated.

RESULTS: A total of 275 patients were included over the 14-year period. Survival to ICU discharge increased from 39.5% in cohort 1 to 53.9% in cohort 3, together with favourable neurological outcome that improved from 30.9 to 42.7%. Adherence to GL recommendations significantly improved across most domains, particularly in haemodynamic management (from 32.0% in cohort 1 to 77.3% in cohort 3), temperature control (from 60.6 to 94.4%), and general ICU management (from 56.3 to 77.6%). Among all interventions, adherence to haemodynamic recommendations was independently associated with improved survival (OR = 2.20, 95% CI: 1.01-4.86).

CONCLUSIONS: Following the implementation of updated post-CA care GLs, adherence to recommendations improved, particularly in haemodynamic management. Although no statistically significant improvements in survival or neurological outcomes were observed, these findings highlight the potential value of sustained GL-based care.

PMID:40601206 | DOI:10.1186/s13613-025-01508-1

Interdiscip Cardiovasc Thorac Surg. 2025 Jul 2:ivaf146. doi: 10.1093/icvts/ivaf146. Online ahead of print.

ABSTRACT

OBJECTIVES: Aortic valve repair procedures for aortic valve regurgitation have been progressively adopted in the last decades. We analysed our results with an external ring annuloplasty and/or leaflet repair.

METHODS: From April 2014 to December 2023, 61 consecutive patients underwent aortic valve repair with external Teflon ring annuloplasty. The external ring was made of an 8 to 9 mm Teflon strip, to reduce the annulus diameter between 21 and 23 mm. Cusp effective height (eH) was assessed with a Caliper (not used before 2018) and any cusp prolapse was corrected by free margin plication, to obtain a 9-10 mm eH for all cusps.

RESULTS: 72.1% of patients had severe aortic regurgitation, associated supracoronary aneurysm repair was performed in 42.6%. No operative death occurred, residual AR more-than-moderate was present in one patient only. Eight years overall survival was 97.4 ± 2.6%, freedom from endocarditis 98.3 ± 1.7% and freedom from thromboembolism 100%. Recurrence of severe aortic regurgitation with need for reoperation was predicted by the presence of particularly enlarged aortic annulus (≥ 28 mm, p < 0.01) and the non-routinary use of cusp caliper (p = 0.03).

CONCLUSIONS: The external Teflon ring annuloplasty appears a safe procedure with high overall survival, freedom from endocarditis and freedom from thromboembolism at ten years. Recurrence of severe aortic regurgitation could be related to patient selection and learning curve.

PMID:40600917 | DOI:10.1093/icvts/ivaf146

Clin Transplant. 2025 Jul;39(7):e70222. doi: 10.1111/ctr.70222.

ABSTRACT

BACKGROUND: Primary graft dysfunction (PGD) represents a leading cause of mortality in patients undergoing donation after brain death (DBD) orthotopic heart transplantation (OHT), requiring timely escalation to mechanical circulatory support. There is a lack of nationwide data regarding PGD after donation after circulatory death (DCD). Here, we evaluated the incidence and short-term outcomes of PGD following DCD.

METHODS: Using the UNOS registry between 9/2023 and 9/2024, we identified all adult (≥18 years) recipients of OHT. The incidence and outcomes of moderate-severe PGD (24- and 72-h post-transplant) were compared between DCD and DBD. Predictors for mortality after PGD were analyzed using Cox proportional hazard models. 30-day survival was analyzed using the Kaplan-Meier method.

RESULTS: A total of 5017 patients underwent first-time OHT, among whom 762 (15.2%) received DCD hearts. DCD had a significantly higher incidence of PGD at 24- (7.9% vs. 4.8%; p = 0.001) and 72-h (5.9% vs. 3.3%; p = 0.001) compared to DBD. 30-day (p = 0.3068) survival was not different between DCD and DBD patients with PGD. Similarly, for recipients with PGD at 72 h, 30-day (p = 0.327) survival was comparable. At 72 h, DCD recipients were more likely to be supported on ECMO (p = 0.016). Transplanting DCD organs did not impact PGD-associated mortality at 24- (HR 0.72, p = 0.442) and 72-h (HR 0.74, p = 0.457). Postoperative ECMO was associated with decreased risk of PGD-associated mortality in DCD recipients at 24- (p < 0.0001) and 72-h (p < 0.0001).

CONCLUSIONS: While PGD rates appear higher in DCD, the associated mortality remains comparable to that of DBD. Early support on ECMO may confer survival benefits in DCD recipients with PGD.

PMID:40600382 | DOI:10.1111/ctr.70222

Clin Transplant. 2025 Jul;39(7):e70223. doi: 10.1111/ctr.70223.

ABSTRACT

BACKGROUND: Recommendations remain unclear between a shorter or extended CMV prophylaxis duration in donor seropositive/recipient seronegative (D+/R-) heart transplant recipients. The purpose of our study is to evaluate the effectiveness of a short (less than 145 days) versus extended (145 days or more) duration of CMV prophylaxis with ganciclovir (GCV)/valganciclovir (VGCV) for prevention of CMV viremia in this high-risk patient population.

METHODS: A retrospective cohort study was conducted of adult (age ≥ 18 years) CMV D+/R- heart transplantation recipients who received intravenous (IV) GCV or oral (PO) VGCV after transplant for CMV prophylaxis. CMV viremia/disease, time to CMV viremia/disease, hospitalizations, and mortality within the first year of transplant were assessed.

RESULTS: A total of 55 D+/R- heart transplant recipients were included in this study, with 28 recipients receiving short duration prophylaxis and 27 recipients receiving extended duration. The median (IQR) duration of therapy for the short and extended duration groups was 76 (69-100) and 189 (168-278) days, respectively. There were similar rates of CMV viremia (35.7% vs. 48.1%; p = 0.35) and CMV disease (10.7% vs. 11.1%, p = 0.96) between the short and extended duration prophylaxis groups. The outcomes of time to CMV from transplant, CMV hospitalization, and mortality were also similar between groups.

CONCLUSION: In the present study, no difference was observed in the incidence of CMV viremia within 1 year between short versus extended duration of GCV/VGCV prophylaxis in CMV D+/R- heart transplant recipients. Prospective studies with a larger sample size may be needed to confirm this finding.

PMID:40600369 | DOI:10.1111/ctr.70223

BMC Biotechnol. 2025 Jul 1;25(1):59. doi: 10.1186/s12896-025-00993-3.

ABSTRACT

Myocardial infarction, characterized by insufficient blood supply to the heart, leads to ischemia and hypoxia of myocardial tissues, causing injury and decreased cardiac function. Despite improvements in pharmaceutical and interventional therapies, it remains a leading cause of death worldwide. Human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in the repair of infarcted myocardium by promoting angiogenesis, reducing inflammation, secreting growth factors and cytokines. However, the harsh hypoxic microenvironment of infarcted myocardial tissue poses a threat to the survival and function of transplanted hUC-MSCs. In this study, we modified the candidate gene promoter of hUC-MSCs under hypoxic conditions and created a promoter that can respond quickly under hypoxic conditions. We found that the modified promoter significantly promoted the transcription efficiency as hypoxia time increased. This indicates that the engineered hypoxia-response promoter can effectively drive gene expression in a hypoxic environment. Furthermore, the transcription efficiency of the modified promoter under normoxic conditions is lower than that of common promoters in eukaryotic organisms, suggesting that this effect can improve the efficacy and safety of hUC-MSC-based myocardial infarction treatment by ensuring that cells function effectively in the damaged hypoxic area.

PMID:40597956 | PMC:PMC12220557 | DOI:10.1186/s12896-025-00993-3

J Heart Lung Transplant. 2025 Jun 30:S1053-2498(25)02054-6. doi: 10.1016/j.healun.2025.06.018. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to evaluate the clinical outcomes of mechanical circulatory support (MCS) using paracorporeal continuous flow (pCF) pumps in children.

METHODS: This multicenter retrospective study used the ACTION database (4/2018-7/2023). Children who were supported with a pCF pump were included. The primary outcome was survival to transplant, explant, or transition to a durable device. The secondary outcomes were adverse events. The outcomes were stratified between non-congenital heart disease (CHD) and CHD with single and biventricular physiology.

RESULTS: 367 patients (CHD, N=204, non-CHD, N=163) were supported with a median of 25 days of support (CHD: 33 vs non-CHD 19 days, P=0.04). CHD included single ventricle (n=135 [66.2%]) and biventricular physiology (n=69 [33.8%]). Non-CHD included dilated cardiomyopathy (n=130[79.8%]), transplant graft dysfunction (n=9 [5.5%]), and others (n=18[11%]). Patients with CHD were younger (0.55 vs. 2.0 years, P=<0.001) and smaller (BSA 0.35 vs. 0.52 m2, P=<0.001, weight 6.7 vs 11.1 kg, P=<0.001) than those without CHD. Overall positive outcome was 77.9% (n=286) [survival to transplant: 38.7 % (n=142), durable device: 22.9% (n=84)], recovery: 16.3% (n=60)]. Between CHD and non-CHD, CHD showed lower positive outcomes (73.0 vs. 82.2%, P=0.05) with higher mortality (24 vs 14.1 %, P=0.02). There were comparable positive outcomes between single and biventricular CHD (73.0%), with a lower recovery rate in single ventricles (8.9% vs 21.8%, P=0.01).

CONCLUSION: Mechanical circulatory support using a pCF pump in children was associated with a positive outcome in 78% of patients in a contemporary cohort. However, patients with CHD patients fared worse than patients without CHD.

PMID:40602507 | DOI:10.1016/j.healun.2025.06.018

Sci Transl Med. 2025 Jul 2;17(805):eadt2426. doi: 10.1126/scitranslmed.adt2426. Epub 2025 Jul 2.

ABSTRACT

Ritscher-Schinzel syndrome (RSS) is a congenital malformation syndrome characterized by cerebellar, cardiac, and craniofacial malformations and phenotypes associated with liver, skeletal, and kidney dysfunction. The genetic cause of RSS remains to be fully defined, and limited information is available regarding the root cause of the multiple tissue phenotypes. Causative mutations in the Commander multiprotein assembly are an emerging feature of this syndrome. Commander organizes the sorting nexin-17 (SNX17)-dependent recycling of hundreds of integral membrane proteins through the endosomal network. Here, we identify previously unrecognized cohorts of patients with RSS that we genetically and clinically analyzed to identify causative genes in the copper metabolic murr1 domain-containing (COMMD) proteins COMMD4, COMMD9, and coiled-coil domain containing 93 (CCDC93) subunits of the Commander complex. Using interactome analysis, we determined that these mutations disrupted Commander assembly and, through cell surface proteomics, that this reduces tissue-specific presentation of cell surface integral membrane proteins essential for kidney, bone, and brain development. We established that these integral proteins contained ΦxNPxY/F or ΦxNxxY/F sorting motifs in their cytoplasmic-facing domains (where Φ is a hydrophobic residue and x is any residue) that are recognized by SNX17 to drive their Commander-dependent endosomal recycling. Last, through generation of mouse models of RSS, we show replication of RSS-associated clinical phenotypes including proteinuria, skeletal malformation, and neurological impairment. Our data establish RSS as a "recyclinopathy" that arises from a dysfunction in the Commander endosomal recycling pathway.

PMID:40601774 | DOI:10.1126/scitranslmed.adt2426

Future Sci OA. 2025 Dec;11(1):2527473. doi: 10.1080/20565623.2025.2527473. Epub 2025 Jul 2.

ABSTRACT

Congenital pulmonary airway malformation (CPAM) and pulmonary sequestration (PS) are among the most common congenital lung malformations and their association is extremely rare. In exceptional cases, patients with CPAM remain asymptomatic until adulthood. We report the case of a 30-year-old man who was hospitalized in our pneumology department for fever, cough and chest pain. Radiological and histological findings confirmed the coexistence of CPAM and PS. The patient underwent surgical resection and recovered well. This is one of the few reported cases in the literature that describe the uncommon association of CPAM and PS with an infrequent diagnosis in adulthood. Clinicians should consider congenital malformations in the differential diagnosis of recurrent respiratory infections, particularly when they affect the same pulmonary lobe.

PMID:40600506 | DOI:10.1080/20565623.2025.2527473

Echocardiography. 2025 Jul;42(7):e70237. doi: 10.1111/echo.70237.

ABSTRACT

We describe a case of congenitally corrected transposition of great arteries (ccTGA) with associated double aortic arch and membranous septal aneurysm. We describe the multimodality imaging features and clinical presentation due to these anomalies.

PMID:40600358 | DOI:10.1111/echo.70237

BMC Med Imaging. 2025 Jul 1;25(1):229. doi: 10.1186/s12880-025-01803-0.

ABSTRACT

BACKGROUND: Single ventricle (SV) Fontan patients are at risk for the development of pathological cervicothoracic lymphatic drainage pathways that are involved in the development of serious conditions such as plastic bronchitis or chylothorax. Visualization and categorization of cervicothoracic lymphatic drainage pathways might therefore help to stratify prognosis and to individualize therapy and follow-up for Fontan patients. This study aimed to show that the 3-dimensional (3D) modified Dixon (mDixon) steady state magnetic resonance (MR) angiography, commonly used to image cardiovascular anatomy, can visualize cervicothoracic lymphatic drainage pathways in high resolution in Fontan patients.

METHODS: 3D mDixon steady state MR angiography of 88 pediatric and young adult patients with a Fontan circulation were retrospectively analysed. The pattern of cervicothoracic lymphatic pathways and image quality according to diagnostic value were assessed. Furthermore, ventricular volumes, mass and ejection fraction from cine imaging were measured.

RESULTS: Image quality was assessed as very good or good in > 90% of the cases. Six patients had a lymphatic complication of which five (83.3%) had a higher cervicothoracic lymphatic pathway type (type 3 or 4).

CONCLUSIONS: 3D mDixon steady state MR angiography is an established method to assess cardiovascular anatomy and function in Fontan patients. The method also allows to visualize and evaluate the cervicothoracic lymphatic anatomy with high image quality. 3D mDixon steady state MR angiography is therefore particularly useful to comprehensively assess Fontan patients, a patient group prone not only to cardiac but also lymphatic failure.

PMID:40597770 | DOI:10.1186/s12880-025-01803-0

Res Pract Thromb Haemost. 2025 May 21;9(4):102897. doi: 10.1016/j.rpth.2025.102897. eCollection 2025 May.

ABSTRACT

BACKGROUND: The incidence of left ventricular thrombus (LVT), a significant complication postacute myocardial infarction (AMI), has seen a decline in the percutaneous coronary intervention era. Patients may not undergo coronary revascularization due to medical contraindications or patient preference.

OBJECTIVES: This study compared post-AMI LVT patients treated with or without revascularization.

METHODS: This was a retrospective study of 263 consecutive post-AMI patients diagnosed with LVT from November 2012 to January 2021, retrieved from an echocardiography database. Patients were stratified by their revascularization status.

RESULTS: Mean (SD) follow-up duration was 2.1 ± 2.1 years. Most post-AMI LVT patients underwent revascularization via percutaneous coronary intervention (71.5%; n = 188). Unrevascularized patients (24.0%; n = 63) were older (P < .001), more often female (P < .001), more comorbid, less likely to have anterior AMI (P < .001), or treated with anticoagulation (P < .001). In multivariable analysis, at least anticoagulation + P2Y12 inhibitor (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.14-2.96; P = .01), but not revascularization (aHR, 1.25; 95% CI, 0.74-2.13; P = .40), was associated with LVT resolution. Both absence of revascularization (aHR, 2.30; 95% CI, 1.09-4.85; P = .03) and LVT resolution (aHR, 6.06; 95% CI, 2.99-12.3; P < .001) were associated with higher mortality after adjusting for age, sex, anemia, anterior AMI, and ejection fraction.

CONCLUSION: Lack of revascularization in post-AMI LVT patients was associated with higher mortality but not LVT resolution. Optimizing medical therapy remains a key treatment goal.

PMID:40599364 | PMC:PMC12210294 | DOI:10.1016/j.rpth.2025.102897

Sci Rep. 2025 Jul 1;15(1):21479. doi: 10.1038/s41598-025-05578-w.

ABSTRACT

Drug-Coated Balloons (DCB) have been widely used in interventional treatment for coronary artery de novo lesions. However, DCB treatment still have a certain proportion of target vessel restenosis (TLR) and adverse follow-up events. Quantitative flow ratio (QFR) loss are important indicators for evaluating long-term vascular functional changes. However, in patients with de novo lesions treated by DCB, the potential risk and protective factors affecting QFR loss remain unclear. The aim of this study was to explore the factors affecting QFR loss in patients with de novo lesion after DCB-angioplasty. Patients who underwent DCB-only intervention de novo lesions and underwent coronary angiography within 12 ± 3 months were enrolled. The QFR loss was defined as difference between the immediate post-procedure QFR and follow-up QFR. The subjects were divided into high QFR loss and low QFR loss groups according to the binary method. The predictors of QFR loss were then analyzed. A total of 115 patients with 1-year follow-up were included in this study, and the median follow-up time was 357 days. Multivariate Logistic analysis showed that patients with diabetes mellitus (OR = 4.937, 95%CI 1.497-16.278, P = 0.009) and LDL-C > 1.8 mmol/L (OR = 2.575, 95%CI 1.021-6.493, P = 0.045) was significantly associated with higher QFR loss 1 year after surgery. In patients undergoing DCB treatment for coronary de novo lesions, diabetes is an independent risk factor for late QFR loss at 1 year. Conversely, achieving LDL-C targets during follow-up is an independent protective factor against late QFR loss at 1 year.

PMID:40594463 | PMC:PMC12216008 | DOI:10.1038/s41598-025-05578-w

Cardiol Plus. 2025 Apr-Jun;10(2):117-128. doi: 10.1097/CP9.0000000000000118. Epub 2025 Jun 30.

ABSTRACT

As ischemic heart disease (IHD) remains the leading cause of mortality worldwide, there is an urgent need for innovative therapies that go beyond symptom management. The irreversible damage to cardiac tissue following myocardial infarction (MI) and the limited regenerative and proliferative capacity of adult cardiomyocytes (CMs) present significant challenges to the development of treatments capable of restoring cardiac function. This review focuses on emerging modified and non-modified messenger ribonucleic acid (mRNA)-based therapies, which offer targeted and transient protein expression. The studies reviewed here address three major therapeutic strategies: cardiac regeneration, aimed at inducing CM proliferation to restore lost cardiac muscle; cardiac protection, centered on anti-apoptotic and anti-inflammatory methods to mitigate further tissue damage; and cardiovascular regeneration, focused on promoting angiogenesis and restoring vascular integrity after injury. By examining mRNA and modified mRNA (modRNA) therapies across these three approaches, this review showcases mRNA's promising role in advancing muscular and vascular regenerative and protective therapeutics for IHD.

PMID:40599555 | PMC:PMC12208384 | DOI:10.1097/CP9.0000000000000118

Nat Commun. 2025 Jul 1;16(1):5902. doi: 10.1038/s41467-025-60934-8.

ABSTRACT

Reactivating the human epicardium post-cardiac injury holds promise for cardiac tissue regeneration. Despite successful differentiation protocols yielding pure, self-renewing epicardial cells from induced pluripotent stem cells (iPSCs), these cells maintain an embryonic, proliferative state, impeding adult epicardial reactivation investigation. We introduce an optimized method that employs mammalian target of rapamycin (mTOR) signaling inhibition in embryonic epicardium, inducing a quiescent state that enhances multi-step epicardial maturation. This yields functionally mature epicardium, valuable for modeling adult epicardial reactivation. Furthermore, we assess cardiac organoids with cardiomyocytes and mature epicardium, probing molecular mechanisms governing epicardial quiescence during cardiac maturation. Our results highlight iPSC-derived mature epicardium's potential in investigating adult epicardial reactivation, pivotal for effective cardiac regeneration. Additionally, the cardiac organoid model offers insight into intricate cardiomyocyte-epicardium interactions in cardiac development and regeneration.

PMID:40593704 | PMC:PMC12216149 | DOI:10.1038/s41467-025-60934-8

Biomed Rep. 2025 Jun 19;23(3):143. doi: 10.3892/br.2025.2021. eCollection 2025 Sep.

ABSTRACT

Diabetic cardiomyopathy (DCM) is an important cause of death in patients with diabetes. DCM can be simulated by cardiomyocyte injury induced by high glucose (HG) in vitro. Scutellarin (Scu) is a flavonoid extracted from Erigeron breviscapus. The H9c2 cell line was used as an in vitro model in the present study to investigate the mechanism by which Scu reduces HG-induced cardiomyocyte injury. Moreover, the present study aimed to provide scientific evidence on the mechanism by which Scu prevents DCM. The following groups were used: Control, model, Scu (50/100/200/400 µM) and curcumin. Following H9c2 cell adherence, the control and model groups were treated with normal medium; the Scu group cells were treated with different concentrations of Scu, whereas the curcumin group cells were treated with 4 µM curcumin for 4 h. Subsequently, the normal group was cultured in normal medium, and the other groups were treated with medium containing 100 mM HG for 48 h. The results indicated that Scu improved the morphology of H9c2 cells treated by HG, enhanced cell proliferative activity, reduced the production of reactive oxygen species and the induction of apoptosis. Moreover, Scu promoted the expression of Bcl-2 and inhibited the expression levels of caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, caspase-12, Bax, NADPH oxidase (Nox)2 and Nox4. The findings indicated that Scu could inhibit oxidative stress and reduce the induction of apoptosis in cardiomyocytes, thereby alleviating HG-induced myocardial injury.

PMID:40599620 | PMC:PMC12209994 | DOI:10.3892/br.2025.2021

Cardiol Plus. 2025 Apr-Jun;10(2):117-128. doi: 10.1097/CP9.0000000000000118. Epub 2025 Jun 30.

ABSTRACT

As ischemic heart disease (IHD) remains the leading cause of mortality worldwide, there is an urgent need for innovative therapies that go beyond symptom management. The irreversible damage to cardiac tissue following myocardial infarction (MI) and the limited regenerative and proliferative capacity of adult cardiomyocytes (CMs) present significant challenges to the development of treatments capable of restoring cardiac function. This review focuses on emerging modified and non-modified messenger ribonucleic acid (mRNA)-based therapies, which offer targeted and transient protein expression. The studies reviewed here address three major therapeutic strategies: cardiac regeneration, aimed at inducing CM proliferation to restore lost cardiac muscle; cardiac protection, centered on anti-apoptotic and anti-inflammatory methods to mitigate further tissue damage; and cardiovascular regeneration, focused on promoting angiogenesis and restoring vascular integrity after injury. By examining mRNA and modified mRNA (modRNA) therapies across these three approaches, this review showcases mRNA's promising role in advancing muscular and vascular regenerative and protective therapeutics for IHD.

PMID:40599555 | PMC:PMC12208384 | DOI:10.1097/CP9.0000000000000118

BMC Med. 2025 Jul 1;23(1):377. doi: 10.1186/s12916-025-04203-x.

ABSTRACT

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is a significant complication following acute myocardial infarction (AMI) and lacks effective therapies. The involvement of gut microbiota in regulating ferroptosis during myocardial I/R injury has not been thoroughly explored. This study aimed to investigate the effect of Lactobacillus on myocardial I/R injury and explore its potential mechanisms.

METHODS: One hundred fifty eight patients with ST-elevation myocardial infarction (STEMI) were enrolled in our prospective observational study. The correlations between Lactobacillus levels and myocardial injury markers, inflammatory factors, oxidative stress, and ferroptosis were evaluated. Furthermore, 30 rats were treated with Lactobacillus or vehicle control for 4 weeks, followed by myocardial I/R surgery. The protective effects of Lactobacillus against I/R injury were assessed by quantifying myocardial apoptosis, inflammation, oxidative stress, and ferroptosis. In addition, the above results were verified in vitro. The signaling pathways were investigated through the knockdown and overexpression of sirtuin 1 (Sirt1) and nuclear factor erythroid 2-related factor 2 (Nrf2).

RESULTS: In clinical study, Lactobacillus levels were significantly negatively correlated with myocardial injury markers, inflammatory factors, and malondialdehyde (MDA), but positively correlated with glutathione (GSH). In rats, Lactobacillus decreased the levels of myocardial injury markers, reduced the size of the myocardial infarction area, ameliorated the disordered myocardial cell arrangement, and improved cardiac function. In both in vivo and in vitro studies, Lactobacillus inhibited cardiomyocyte apoptosis by upregulated B-cell lymphoma-2 (Bcl-2), downregulated Bcl-2 associated X (Bax), and caspase-3. Furthermore, Lactobacillus decreased inflammatory factors, MDA, reactive oxygen species (ROS) levels, and increased superoxide dismutase (SOD) activity. For ferroptosis, Lactobacillus upregulated the expression of glutathione peroxidase 4 (GPX4) and downregulated the expressions of acyl-CoA synthetase long-chain family member 4 (ACSL4) and transferrin receptor protein 1 (TfR1). Finally, knockdown and overexpression of Sirt1 and Nrf2 in vitro demonstrated that Lactobacillus exerted the effect by upregulating the Sirt1/Nrf2/HO-1 pathway.

CONCLUSIONS: Our findings reveals that Lactobacillus protects against myocardial I/R injury by inhibiting apoptosis, inflammation, oxidative stress, and ferroptosis through the Sirt1/Nrf2/HO-1 signaling axis, suggesting a novel probiotic-based therapeutic potential for I/R injury.

PMID:40598393 | PMC:PMC12218948 | DOI:10.1186/s12916-025-04203-x

BMC Cancer. 2025 Jul 1;25(1):1063. doi: 10.1186/s12885-025-14280-z.

ABSTRACT

BACKGROUND: Endocrine therapies, including tamoxifen (TMX) and aromatase inhibitors (AIs), are widely used in breast cancer treatment. This study aims to evaluate the cardiovascular risks associated with these therapies in different age groups of non-metastatic breast cancer patients.

METHODS: We conducted a cohort study using data from patients newly diagnosed with non-metastatic breast cancer. Patients were categorized into two ages (< 45 years and > 55 years) and then divided into groups based on whether they were newly receiving either TMX or AI. Follow-up continued until the first occurrence of a study outcome, death, or the last date of data collection (December 31, 2022). Primary outcomes were coronary artery disease, myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiovascular mortality, all-cause mortality, and major adverse cardiovascular events (MACE).

RESULTS: Among patients < 45 years old, 2837 were newly treated with TMX (n = 2370) or AI (n = 467). During a median follow-up of 8.4 years, the incidence rates of coronary artery disease (5.6 vs. 6.6 per 1000 person-years), myocardial infarction (1.0 vs. 1.7 per 1000 person-years), ischemic stroke (1.5 vs. 1.5 per 1000 person-years), and cardiovascular mortality (1.4 vs. 1.5 per 1000 person-years) were similar between TMX and AI users, with no significant differences in hazard ratios or cumulative incidence curves. However, AI users had a higher risk of HHF (Weighted HR, 3.08 [95% CI, 1.54-6.13], P = 0.001) and AF (P = 0.039) compared to TMX users. For MACE, there was a non-significant elevated risk (Weighted HR, 1.59 [95% CI, 0.90-2.81]), suggesting a trend toward increased risk. Among patients > 55 years old, 11,846 were newly treated with TMX (n = 6577) or AI (n = 5269). During a median follow-up of 5.0 years, AI users had a significantly increased risk of primary cardiovascular outcomes, including CAD, MI, ischemic stroke, HHF, AF, cardiovascular mortality, and MACE (all P < 0.01).

CONCLUSION: The study indicates that AIs are linked to a higher risk of cardiovascular events in post-menopausal patients compared to TMX. In younger patients, TMX's protective effect on cardiovascular outcomes may be less pronounced. Further large-scale studies are required to corroborate and address limitations related to menopausal status and residual confounding.

PMID:40597894 | DOI:10.1186/s12885-025-14280-z