J Biochem Mol Toxicol. 2025 Jul;39(7):e70365. doi: 10.1002/jbt.70365.
ABSTRACT
This systematic review and meta-analysis were conducted to evaluate the therapeutic efficacy of Astragaloside IV (As-IV) in ischemic heart disease based on the preclinical evidence and to correlate the cardioprotective effect with various available mechanisms. This systematic review and meta-analysis were conducted based on the results of a thorough literature search in databases of published papers, such as PubMed, Embase, and Google Scholar. A total of 18 studies that met the inclusion/exclusion criteria were included. The meta-analysis has shown the significant therapeutic efficacy of As-IV on ischemic heart disease. As-IV has decreased the myocardial infarction size, the left ventricular weight indices, the left ventricular internal diameter in systole, and the left ventricular internal diameter in diastole. As-IV has decreased the level of the third type of collagen and the decreased activity of creatine kinase and lactate dehydrogenase. Also, As-IV has markedly decreased the rate of apoptosis and the expression of the proapoptotic markers such as caspase-3 and Bax. The left ventricular systolic pressure, as well as the arterial shortening edge and the ejection fraction, has increased. The levels of the antiapoptotic protein Bcl-2 increased. In addition, As-IV has a powerful anti-inflammatory influence by inhibiting the main markers of inflammation, such as TLR4, IL-1, TNF-α, and TGF-β. As-IV has also caused an effect on angiogenesis by increasing the VEGF level. The results have revealed the As-IV, as a decent universal medicine for ischemic heart disease because of its variety of actions and effectiveness.
PMID:40551496 | PMC:PMC12186012 | DOI:10.1002/jbt.70365
J Med Food. 2025 Jun 24. doi: 10.1089/jmf.2025.k.0031. Online ahead of print.
ABSTRACT
Doxorubicin (DOX), an anthracycline-based anticancer drug, is commonly used to treat various cancers, but its prolonged use may lead to cardiotoxicity. Despite extensive research efforts, effective strategies for managing DOX-induced cardiotoxicity (DICT) remain limited. This study investigated the DICT-inhibitory efficacy of the water extract of Allium victorialis L. (AVE) and its underlying mechanism. AVE protected mouse cardiomyocytes, H9c2 cells, from DOX-induced toxicity while not interfering with DOX's cytotoxic effect on the MDA-MB-231 cells, human breast cancer cells. DOX-induced abnormal heart rate, RR interval, cQT prolongation, and segmentation were normalized following AVE supplementation. Also, AVE reduced the serum levels of creatine kinase and lactate dehydrogenase and suppressed myocardial fibrosis and cell death by DICT in the AVE-fed mice group. Moreover, AVE was shown to restore DOX-induced impaired electrophysiological changes in human-induced pluripotent stem cell-derived cardiomyocytes, including reduced total activity and decreased conduction velocity, while also normalizing the beat period irregularity and beat period mean. A total of 57 metabolites were tentatively identified in the AVE sample. Furthermore, PCR microarray and western blot analyses confirmed that AVE reversibly increased the expression of antioxidant-related genes and proteins. Altogether, the antioxidant properties of AVE could be utilized as a new strategy for preventing and treating DICT.
PMID:40551413 | DOI:10.1089/jmf.2025.k.0031
J Cardiothorac Surg. 2025 Jun 24;20(1):272. doi: 10.1186/s13019-025-03505-8.
ABSTRACT
OBJECTIVE: To explore the application and effect of aortic annulus reconstruction (AAR) with bovine pericardium during surgical aortic valve replacement (SAVR) for severe calcific aortic stenosis (AS).
METHODS: We retrospectively reviewed 12 patients with severe calcified AS who underwent bovine pericardium aortic annulus reconstruction between January 2021 to December 2023. The average age of the patients was 58 ± 8.8 years. All patients were diagnosed with severe AS, along with aortic valve and annulus calcification, through chest computed tomography (CT) and transthoracic echocardiography (TTE) prior to surgery. After the resection of severely calcified aortic annulus tissue, all patients were given a bovine pericardial patch to repair the annular defect, and five of these patients underwent Y-incision aortic annular enlargement (AAE). The patients were followed up for a duration of 0.5 to 2 years.
RESULTS: A total of 12 patients undergoing SAVR were enrolled, and all received bovine pericardial patches to repair the annular defects, with a mean preoperative indexed effective orifice area (iEOA) of 0.58 ± 0.098 cm²/m². The average extracorporeal circulation time during the operation was 150.83 ± 34.5 min, and the average cross-clamp time was 95.42 ± 17.46 min. Postoperative evaluations indicated that the structural integrity of the valve annulus remained intact, demonstrating hemodynamic stabilization without any recorded fatalities among participants. Compared to preoperative levels, the aortic valve mean gradient (4.67 ± 1.15 vs. 59.67 ± 17.94 mmHg, P < 0.001), peak gradient (13 [10-15.75] vs. 92 [82.25-110.25] mmHg, P < 0.001), mean aortic jet velocity (99.67 ± 15.44 vs. 367.17 ± 58.13 cm/s, P < 0.001), and peak aortic jet velocity (182.25 ± 23.40 vs. 495.67 ± 61.74 cm/s, P < 0.001) significantly decreased after 0.5 years of follow-up. There were no complications such as hemolysis, perivalvular leakage, thrombosis or endocarditis during follow-up.
CONCLUSION: In patients with severe calcified AS, the AAR technique using bovine pericardium during SAVR is safe and effective, with stable hemodynamic performance and satisfactory clinical outcomes.
PMID:40556029 | PMC:PMC12186314 | DOI:10.1186/s13019-025-03505-8
Cell Death Differ. 2025 Jun 24. doi: 10.1038/s41418-025-01540-5. Online ahead of print.
ABSTRACT
Activation of the intrinsic regenerative potential of adult mammalian hearts by promoting cardiomyocyte proliferation holds great potential in heart repair. CAND1 (Cullin-associated and neddylation-dissociated protein 1) functions as a critical regulator of cellular protein homeostasis by fine-tuning the ubiquitinated degradation of specific abnormally expressed protein substrates. Here, we identified that cardiac-specific transgenic overexpression of CAND1 reduced the infarct size, restored cardiac function, and promoted cardiomyocyte proliferation after myocardial infarction in juvenile (7-day-old) and adult (8-week-old) mice. Conversely, CAND1 deficiency blunted the regenerative capacity of neonatal hearts after apex resection. MS and functional verification demonstrated that CAND1 enhanced the assembly of Cullin1, FBXW11(F-box/WD repeat-containing protein 11), and Mob1b (Mps one binder kinase activator 1b) complexes, and thus promotes the degradation of Mob1b. The ubiquitination of Mob1b occurred at K108 and was linked by K48 of ubiquitin. Mob1b deletion partially rescued the loss of regenerative capacity in neonatal hearts induced by CAND1 deficiency and improved cardiac function in adult mice post-MI. Moreover, CAND1 promoted the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our data demonstrate that CAND1 promotes cardiomyocyte proliferation via FBXW11-mediated K48-linked ubiquitination degradation of Mob1b, and improves heart regeneration after cardiac injury. The findings provide a novel strategy to promote cardiac regeneration and repair. Schematic diagram of the role of CAND1 in regulating ubiquitination and degradation of Mob1b and cardiomyocyte proliferation and heart regeneration. Under CAND1-High condition, CAND1 promotes the incorporation of Cullin1, FBXW11, and Mob1b complexes, and accelerates SCFFBXW11-mediated K48-linked ubiquitination of Mob1b at the K108 site, which leads to the degradation of Mob1b and thus suppresses the Hippo signaling pathway and facilitates cardiomyocyte proliferation and heart regeneration post-MI.
PMID:40555744 | DOI:10.1038/s41418-025-01540-5
Exp Mol Med. 2025 Jun 24. doi: 10.1038/s12276-025-01472-7. Online ahead of print.
ABSTRACT
Barth syndrome (BTHS) is an ultrarare, infantile-onset, X-linked recessive mitochondrial disorder that primarily affects males, owing to mutations in TAFAZZIN, which catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mitochondrial transplantation is a novel technique to treat mitochondrial dysfunction by delivering healthy mitochondria to diseased cells or tissues. Here we explored the possibility of using stem-cell-derived cardiomyocytes as a source of mitochondrial transplantation to treat BTHS. We established induced pluripotent stem (iPS) cells from healthy individuals and from patients with BTHS and differentiated them into cardiomyocytes. The iPS-cell-differentiated cardiomyocytes (CMs) derived from patients with BTHS exhibited less expression of cardiomyocytes markers, such as α-SA, cTnT and cTnI, and smaller cell size than normal iPS-cell-derived CMs. Multielectrode array analysis revealed that BTHS CMs exhibited shorter beat period and longer field potential duration than normal CMs. In addition, mitochondrial morphology and function were impaired and mitophagy was decreased in BTHS CMs compared with normal CMs. Transplantation of mitochondria isolated from normal CMs induced mitophagy in BTHS CMs, mitigated mitochondrial dysfunction and promoted mitochondrial biogenesis. Furthermore, mitochondrial transplantation stimulated cardiac maturation and alleviated cardiac arrhythmia of BTHS CMs. These results suggest that normal CMs are useful for allogeneic transplantation in the treatment of mitochondrial diseases, including BTHS.
PMID:40555742 | DOI:10.1038/s12276-025-01472-7
J Cardiothorac Vasc Anesth. 2025 May 18:S1053-0770(25)00413-6. doi: 10.1053/j.jvca.2025.05.031. Online ahead of print.
ABSTRACT
OBJECTIVES: To assess concordance between Hemochron Response (ACTr) and the three-activator device Hemochron Signature Elite (ACTe) in adult cardiac surgery patients. To evaluate the correlation between ACTe and anti-Xa values.
DESIGN: Multicenter, prospective observational study.
SETTING: University hospitals.
PARTICIPANTS: Thirty-five elective adult cardiac surgery patients.
INTERVENTIONS: Patients received 300 IU/kg of unfractionated heparin (UFH) before cardiopulmonary bypass (CPB), as recommended by guidelines. ACTe was the reference device, with ACTe target ≥ 450 seconds required to establish adequate anticoagulation during CPB. Otherwise, an additional 100 IU/kg UFH was administered, up to a maximum cumulative dose of 500 IU/kg. Blood samples for ACTe and ACTr and samples for anti-Xa activity were collected simultaneously at baseline and after each UFH administration. The analyses included Pearson correlation, linear regression, and the Bland-Altman test.
MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were enrolled (71% male, median age 68 years). After 300 IU/kg UFH, 13 (37%) patients required a second heparin dose due to ACTe less than 450 seconds despite ACTr ≥ 450 seconds and 5 (14%) due to ACT less than 450 seconds with both devices. Following the second UFH administration, 10/18 (55%) patients still did not reach the target ACTe despite an ACTr ≥ 450 seconds, requiring a third UFH administration. ACTe and ACTr showed no correlation (r = 0.157, p = 0.369). Linear regression analysis demonstrated limited agreement (R2 = 0.025). Bland-Altman analysis indicated a mean bias of -20.7% (95% CI -75.28% to +35.5%), with ACTe underestimating ACTr. The predicted ACTe, corresponding to an ACTr threshold of 450 seconds, was 357 seconds. Anti-Xa levels always exceeded 4 IU/mL, confirming adequate anticoagulation in all cases and were positively correlated to ACTe (r = 0.587, p < 0.001). Predicted ACTe interval corresponding to anti-Xa levels of 4 IU/mL was 263 to 515 seconds.
CONCLUSIONS: ACTe and ACTr showed no correlation. Switching devices without adjusting ACT thresholds leads to unnecessary UFH redosing, despite adequate anticoagulation as measured by anti-Xa levels.
PMID:40555631 | DOI:10.1053/j.jvca.2025.05.031
Transplant Proc. 2025 Jun 23:S0041-1345(25)00305-7. doi: 10.1016/j.transproceed.2025.05.030. Online ahead of print.
ABSTRACT
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic option for hematologic malignancies. However, it is associated with severe complications, including graft-versus-host disease (GVHD). While GVHD is widely recognized for its impact on various organs, its role in the development of heart failure (HF) remains insufficiently understood. This study investigates the association between GVHD and HF following allo-HSCT, focusing on identifying key risk factors contributing to HF development.
METHODS: A retrospective cohort study was conducted on 220 patients who underwent allo-HSCT between 2005 and 2024. HF was defined by clinical criteria and left ventricular ejection fraction. The association of GVHD severity (acute and chronic), inflammatory markers (tumor necrosis factor-alpha, interleukin-6), and cardiac biomarkers (B-type natriuretic peptide) with HF was analyzed. Multivariate logistic regression was performed to identify independent predictors of HF.
RESULTS: Patients with HF demonstrated significantly lower left ventricular ejection fraction (33.92% ± 6.73% vs 61.51% ± 6.18%, P = .021) and higher levels of B-type natriuretic peptide (393.29 ± 71.29 ng/L vs 307.92 ± 76.28 ng/L, P = .042), tumor necrosis factor-alpha (80.3 ± 20.4 pg/mL vs 40.2 ± 10.1 pg/mL, P < .001), and interleukin-6 (65.1 ± 15.7 pg/mL vs 25.4 ± 8.6 pg/mL, P < .001) compared to controls. Severe acute GVHD (Grade ≥III) significantly increased the risk of HF (odds ratio = 3.5, P < .001). Patients with multiple GVHD-related complications had a 3.6-fold higher likelihood of HF development (P < .01). Echocardiographic findings revealed significant cardiac remodeling in HF patients, with increased left ventricular end-diastolic diameter (68.76 ± 7.23 mm vs 44.18 ± 7.16 mm, P = .004) and left ventricular posterior wall thickness (12.18 ± 4.32 mm vs 4.46 ± 2.19 mm, P = .002). Additionally, HF patients experienced more severe transplant-related complications, including infections (29.0% vs 10.6%, P = .041) and hemorrhagic cystitis (23.4% vs 7.1%, P = .027). Mortality was significantly higher in the HF group (86.0% vs 41.6%, P < .001), with infection (71.0%) and HF (21.5%) being the leading causes of death. GVHD significantly heightens the risk of HF after allo-HSCT.
CONCLUSIONS: These findings underscore the necessity for proactive cardiovascular monitoring and targeted therapeutic interventions in GVHD patients to prevent the development of HF.
PMID:40555592 | DOI:10.1016/j.transproceed.2025.05.030
J Card Fail. 2025 Jun 17:S1071-9164(25)00251-9. doi: 10.1016/j.cardfail.2025.05.015. Online ahead of print.
ABSTRACT
BACKGROUND: The impact of amiodarone on severe primary graft dysfunction (PGD) and vasoactive inotropic scores (VIS) following heart transplantation (HT) is unclear.
METHODS AND RESULTS: We investigated these relationships through a retrospective study of 183 consecutive patients > 18 years old who underwent isolated HT at our center from 2018-2023. Data for amiodarone use in the 6 months pre-HT were recorded (duration, cumulative dose, use at HT, last dose pre-HT). Of the 69 patients in the amiodarone cohort, 37 were considered to be on amiodarone at time of transplant. The primary endpoint was severe PGD as defined by International Society of Heart and Lung Transplantation (ISHLT) criteria. Post-HT VIS were calculated as defined by ISHLT.
CONCLUSIONS: Amiodarone was not associated with severe PGD (p = 0.67), and there was no difference in post-transplant VIS based on amiodarone exposure (20 [19.6] vs 16.3 [13.8], p=0.122, Figure 1). This study supports similar hemodynamic profiles post-HT regardless of amiodarone use.
PMID:40553932 | DOI:10.1016/j.cardfail.2025.05.015
Proc Natl Acad Sci U S A. 2025 Jul;122(26):e2424534122. doi: 10.1073/pnas.2424534122. Epub 2025 Jun 24.
ABSTRACT
Tissue fibrosis is commonly associated with organ malfunction and is strongly associated with the development of chronic rejection, cardiovascular diseases, and other chronic diseases. Fibrosis also contributes to immune exclusion in tumor tissues. Targeting fibrosis might be a strategy for prolonging allograft survival while suppressing cancer development. Here, single-cell transcriptomes of human and mouse heart allografts showed that macrophages accumulated in grafts with fibrosis were reprogrammed via histone methylation regulated by Setdb1, an H3K9 methyltransferase. Myeloid-specific deletion of Setdb1 prolonged heart allograft survival but reversed immune exclusion in tumor tissues. Interestingly, myeloid-specific Setdb1-knockout led to lower fibrosis in heart allografts and tumor tissues in mice. Our single-cell sequencing data showed that Setdb1 ablation impaired Fn1+ and SPP1+ profibrogenic macrophage reprogramming. Mechanistically, Fn1, which was induced by the CCR2-Creb/Setdb1 axis, upregulated the expression of genes related to fibrosis in fibroblasts and macrophages via ITGA5 and PIRA receptors. Blocking the interaction between FN1 and these receptors inhibited fibrosis in allograft and tumor tissues. Our results reveal a target, histone methylation in macrophages, for the treatment of fibrosis-related disease.
PMID:40553495 | DOI:10.1073/pnas.2424534122
Scand Cardiovasc J. 2025 Jun 24:1-11. doi: 10.1080/14017431.2025.2525098. Online ahead of print.
ABSTRACT
OBJECTIVE: The aim was to resuscitate and evaluate hearts ex vivo after 22 minutes of cardiac arrest with the goal of increasing the number of usable hearts from controlled donation after circulatory death (cDCD).
DESIGN: Eight pigs (39-61 kg) underwent 22 minutes of ventricular fibrillation, after which the heart was first perfused in vivo for three minutes with an oxygenated, erythrocyte-containing cardioplegic preservation solution. The heart was then explanted and perfused ex vivo with the same solution for three hours at 18 °C in a transportable heart preservation system. Functional evaluation was performed ex vivo (n = 7), while one heart underwent orthotopic transplantation and was monitored for 24 hours.
RESULTS: The seven hearts evaluated ex vivo easily pumped twice the cardiac output measured in vivo. The transplanted heart maintained normal blood pressure, blood gases, and urine output throughout the 24-hour observation period. At the end of this period the aortic pressure was 104/80 mmHg with a heart rate of 129 beats per minute. Intravenous administration of 20, 40, and 100 µg adrenaline resulted in an aortic pressures of 238/171, 284/196, and 287/201 mmHg with corresponding heart rates of 162, 188, and 223 beats per minute.
CONCLUSION: Hearts exposed to 22 minutes of cardiac arrest were successfully resuscitated ex vivo and demonstrated adequate function when evaluated.
PMID:40553492 | DOI:10.1080/14017431.2025.2525098
Clin Transplant. 2025 Jul;39(7):e70213. doi: 10.1111/ctr.70213.
ABSTRACT
INTRODUCTION: The impact of empiric intraoperative vancomycin and piperacillin-tazobactam (VPT) compared to vancomycin and cefepime (VC) on AKI is equivocal, and renal recovery and infection outcomes have not been studied in this context. Further, this has not been studied in patients undergoing orthotopic heart transplantation (OHT).
METHODS: We performed a single-center prospective study in patients undergoing OHT (n = 120), with a change in intraoperative microbial coverage from VPT to VC. Primary outcomes included AKI rates and stage. Secondary outcomes included renal recovery rates, bloodstream bacterial infections, rates of enterococcal infection, ESRD (end-stage renal disease), change in eGFR, and mortality at 12 months post-OHT.
RESULTS: Rates of all stages of AKI were similar between groups (p = 0.769), and the majority of AKI in both groups were Stage 1. 27.1% of patients in the pre-intervention arm and 25.0% in the post-intervention arm had a Stage 3 AKI (p = 0.798). Rates of recovery from AKI at 7 days showed a trend toward improved recovery in patients receiving VC compared to VPT (65.1%, 46.7%, p = 0.056), but recovery from RRT at 7 days and recovery from RRT at hospital discharge were not statistically significant between groups (p = 0.140, p = 0.659). Rates of bloodstream infection were similar following the change in empiric antimicrobials (2.08%, 4.17%; p = 0.53), and rates of wound infection were similar following this change (4.2%, 1.4%; p = 0.56). There was no increase in enterococcal infections.
CONCLUSION: In patients undergoing OHT and receiving empiric antimicrobial therapy, change from VPT to VC did not affect the incidence or severity of AKI, renal recovery, or infection rates.
PMID:40552693 | PMC:PMC12186467 | DOI:10.1111/ctr.70213
Clin Transplant. 2025 Jul;39(7):e70217. doi: 10.1111/ctr.70217.
ABSTRACT
INTRODUCTION: Primary graft dysfunction (PGD) is a significant barrier to survival in lung transplant (LTx) recipients. PGD in patients with systemic sclerosis (SSc) remains especially underrepresented in research.
METHODS: We investigated 92 SSc recipients (mean age 51 years ± 10) who underwent bilateral LTx between 2007 and 2020. PGD was defined as grade 3 PGD at 72 h post-LTx. A comprehensive set of CT image features was automatically computed from recipient chest CT scans using deep learning algorithms. Volumetric analysis of recipients' lungs and chest cavity was used to estimate lung-size matching. Four machine learning (ML) algorithms were developed to predict PGD, including multivariate logistic regression, support vector machine (SVM), random forest classifier (RFC), and multilayer perceptron (MLP).
RESULTS: PGD was significantly associated with BMI >30 kg/m2 (p = 0.009), African American race (p = 0.011), lower Preop FEV1 (p = 0.002) and FVC (p = 0.004), longer waitlist time (p = 0.014), higher lung allocation score (LAS) (p = 0.028), and interstitial lung disease (p = 0.050). From CT analysis, PGD was significantly associated with decreased lung volume (p < 0.001), increased heart-chest cavity volume ratio (p < 0.001), epicardial (p = 0.033) and total heart (p = 0.049) adipose tissue, and five cardiopulmonary features (p < 0.050). Oversized donor allografts estimated using CT analysis were significantly associated with PGD (p < 0.050). The MLP model achieved a maximum AUROC of 0.85 (95% CI: 0.81-0.88) in predicting PGD with four features: Preop FEV1, heart-chest cavity volume ratio, waitlist time, and donor to recipient chest cavity volume ratio.
CONCLUSION: CT-derived features are significantly associated with PGD, and models incorporating these features can predict PGD in SSc recipients.
PMID:40552679 | DOI:10.1111/ctr.70217
Artif Organs. 2025 Jun 24. doi: 10.1111/aor.15035. Online ahead of print.
NO ABSTRACT
PMID:40552484 | DOI:10.1111/aor.15035
Future Cardiol. 2025 Jun 24:1-6. doi: 10.1080/14796678.2025.2521993. Online ahead of print.
ABSTRACT
Xenotransplantation is a promising advancement in the field of transplantation that could eliminate deaths on the waitlist and provide an unlimited supply of on-demand organs for those in need of this life-saving therapy. The results of preclinical studies in orthotopic heart xenotransplantation have shown that non-human primate models can consistently survive 9 months post-transplant. However, early clinical results in orthotopic heart xenotransplantation have been subpar compared to traditional orthotopic heart transplantation as the longest surviving patient survived for 60 days with a complicated postoperative course. Partial heart xenotransplantation could serve as an earlier clinical use case of xenotransplantation products due to the many advantages of the neonate and infant population for xenotransplantation as well as the unique immunogenicity of heart valves which is significantly lower than that of whole hearts. The adoption of partial heart xenotransplantation would allow more children to realize the benefits of a valve that tolerates somatic growth without the need for serial reoperation.
PMID:40552429 | DOI:10.1080/14796678.2025.2521993
Front Oncol. 2025 Jun 9;15:1568169. doi: 10.3389/fonc.2025.1568169. eCollection 2025.
ABSTRACT
Acquired aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and decreased hematopoietic stem and progenitor cells (HSPCs) in the bone marrow, it can be either congenital or acquired, predominantly affecting adolescents and the elderly, with higher incidence in Asia compared to Europe and America. Current treatment options include allogeneic hematopoietic stem cell transplantation or immunosuppressive agents, yet proximately a third of patients fail to reach long-term survival. AA is primarily driven by immune-mediated destruction of HSPCs, initiated by self-activated T cells. Early stages feature a Th1 response, which later shifts to Th17 and effector memory CD8+ T cells. Key cytokines including interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) play crucial roles in this immune dysregulation, influencing HSPCs and contributing to bone marrow failure. Furthermore, bone marrow macrophages (MΦ), particularly M1 subtype, are implicated in AA via the TNF-α/TNF-α receptor pathway, leading to T cell activating and subsequent HSPC damage. Interestingly, MΦ with high expression of IL-27Ra have been demonstrated to contribute to HSPC destruction in AA murine models. Beyond their role in thrombosis, platelets also participate in immune regulation. Some studies suggest that platelet may modulate T cell responses through mechanisms such as Akt-PGC1α-TFAM pathway or PF4-mediated activity, which could play a role in AA. However, direct evidence connecting platelet regulation to T cell-mediated HSPC damage is limited, and current research has largely focuses on CD8+ T cells. Moving forward, it is essential to investigate the interactions between platelets, CD4+ T cells, and mitochondrial energy metabolism. In this review, we propose that platelet-derived factors such as PF4 and TGFβ may activate mitochondrial pathways, influencing T cell activation and leading to HSPC destruction in AA. This hypothesis could provide new insights into the molecular mechanisms of AA and pave the way for novel therapeutic strategies (Highlight).
PMID:40552264 | PMC:PMC12183292 | DOI:10.3389/fonc.2025.1568169
Xenotransplantation. 2025 May-Jun;32(3):e70058. doi: 10.1111/xen.70058.
ABSTRACT
INTRODUCTION: Xenotransplantation has emerged as a promising solution to organ shortage, generating numerous publications. However, no studies have analyzed the research dynamics of xenotransplantation research. We aimed to systematically assess xenotransplantation publication activity.
METHODS: A systematic literature search was conducted up to November 22, 2024. Studies on xenotransplantation of solid organs and islets of Langerhans from animals to humans, or perfusion with human blood or its derivatives were included. Publication information, publishing journal, publication type, organ, donor species, and topics studied were extracted.
RESULTS: Of 2944 publications, 706 met inclusion criteria: 41.2% original articles, 41.1% reviews, 14.2% publications without original data, 1.6% case reports, 1.3% research letters, 0.6% systematic reviews/meta-analyses. Publication activity displayed two peaks: in the 1990s, driven by the gene editing advancements, and in the early 2020s, following the first pig-to-human transplantation. The top five publishing countries were the USA with (48.2%), Germany (10.2%), UK (5.4%), Sweden (4.8%), and China (4.2%). Xenotransplantation journal accounted for 19.7% of publications, transplantation journals for 27.6%, and general medical journals for 5.4%. Islets of Langerhans were studied in 23.1% of studies, and the most studied organs were heart (21.2%), followed by kidney (17.1%), liver (12.2%), and lung (6.2%). The most represented thematic groups were rejection, immune mechanisms, overall challenges, gene editing, current research, and prospects.
CONCLUSION: This first systematic assessment of xenotransplantation research highlights its growing global interest and evolving focus areas. The low proportion of publications with original data underscores the need for more original research. Limited representation in general medical journals highlights the importance of engaging a broader audience as clinical trials approach.
PMID:40551623 | DOI:10.1111/xen.70058
Eur J Pediatr. 2025 Jun 25;184(7):440. doi: 10.1007/s00431-025-06187-5.
ABSTRACT
The role of intrarenal Doppler parameters in predicting postoperative acute kidney injury (AKI) has been increasingly emphasized, but remains underexplored in children undergoing cardiac surgery. This study aimed to investigate the association between intrarenal venous Doppler patterns and the occurrence of postoperative AKI in children after congenital cardiac surgery. This retrospective study included 338 pediatric patients who underwent elective cardiac surgery between June 2019 and December 2021. Intrarenal blood flow Doppler measurements were performed before and after surgery. The primary outcome was the difference in postoperative renal venous Doppler patterns between patients with and without AKI according to the Kidney Disease: Improving Global Outcomes criteria. Multivariate logistic regression analysis was performed to identify factors associated with AKI. Of the 338 patients, 12.1% developed postoperative AKI. Patients with AKI had a higher prevalence of biphasic and monophasic renal venous flow patterns than those without AKI (63.5% vs. 19.9%, p < 0.001). The AKI group had higher pre- and postoperative renal resistive index than the non-AKI group. Discontinuous renal venous flow pattern, preoperative intensive care unit admission, higher Risk Adjustment for Congenital Heart Surgery-1 score and intraoperative vasoactive-inotropic score, and lower preoperative albumin levels were associated with postoperative AKI. Conclusion: Abnormal postoperative intrarenal venous Doppler patterns were associated with AKI in pediatric patients after congenital cardiac surgery. Intraoperative Doppler assessment of renal venous flow may help identify children at a higher risk of AKI, allowing for early interventions.
PMID:40555869 | PMC:PMC12187880 | DOI:10.1007/s00431-025-06187-5
Leg Med (Tokyo). 2025 Jun 22;76:102661. doi: 10.1016/j.legalmed.2025.102661. Online ahead of print.
ABSTRACT
Stab injuries involving the vertebral region are rare and pose significant challenges during forensic autopsy due to the complexity of the surrounding anatomical structures. Radiological techniques, such as post-mortem computed tomography (PMCT) or micro-CT, have shown great potential for detecting and detailing sharp bone lesions. We herein present a fatal case of homicidal stab wound involving the left vertebral artery and the homolateral surface of the axis. PMCT identified a fracture of the left lateral mass of the axis (C2), and micro-CT revealed a cortical discontinuity of the left transverse process of C2, nearly separating the transverse process from the body of the axis. Based on micro-CT data, a 3D model of the first three cervical vertebrae was printed in a clear material on a Formlabs Form 3L printer, and a fit-matching analysis was conducted with two potential weapons. The billhook seized by the Police demonstrated a precise fit with the fracture pattern when its handle was positioned posteriorly, and the tip penetrated laterally in a left-to-right trajectory. In conclusion, to the best of our knowledge, this is the first report of vertebral stab wound analysis using a combined micro-CT and 3D printing approach. Although 3D printing is not yet a fully validated forensic method, and further research is needed for identifying any potential errors occurring during production, segmentation, stereolithography data generation, and post-processing, this report highlights the high potentiality of micro-radiology and 3D printing as promising tools for the morphometric analysis of vertebral injuries.
PMID:40554891 | DOI:10.1016/j.legalmed.2025.102661
Gen Thorac Cardiovasc Surg. 2025 Jun 24. doi: 10.1007/s11748-025-02172-9. Online ahead of print.
ABSTRACT
BACKGROUND: Pulmonary sequestration (PS) is a rare congenital lung malformation often requiring surgical resection due to recurrent infections or hemoptysis. Traditionally treated via open thoracotomy, recent advancements have made minimal-invasive approaches like robotic-assisted thoracoscopic surgery (RATS) increasingly viable. This study compares outcomes between RATS and open resection for PS in a high-volume center.
METHODS: In this retrospective cohort study, 23 adult patients who underwent surgical resection of PS between 2010 and 2023 were analyzed. Fifteen patients were treated via open thoracotomy (THKT), while eight underwent RATS using the DaVinci-X system. We compared preoperative findings, intraoperative variables, and postoperative outcomes.
RESULTS: The patients in the RATS group were younger (median age: 36 vs 47 years) and had a shorter median hospital stay (5 vs 10 days, p < 0.001) compared to the THKT group. The RATS group also experienced earlier chest drainage removal (3 vs. 4 days, p = 0.016). However, the median duration of surgery was longer for RATS (118 vs. 75 min, p = 0.018). A trend towards less postoperative complications was observed in the RATS group (33% vs. 0%).
CONCLUSIONS: RATS provides a safe and effective alternative to open surgery for PS resection, with benefits including reduced hospital stay and earlier chest tube removal. Despite longer operative times, the minimally invasive approach may offer enhanced recovery and fewer complications. Continued accumulation of experience with RATS is likely to improve operative efficiency, making it a valuable option in the surgical management of pulmonary malformations.
PMID:40553225 | DOI:10.1007/s11748-025-02172-9
Front Pharmacol. 2025 Jun 9;16:1633008. doi: 10.3389/fphar.2025.1633008. eCollection 2025.
ABSTRACT
[This corrects the article DOI: 10.3389/fphar.2024.1449831.].
PMID:40552163 | PMC:PMC12183511 | DOI:10.3389/fphar.2025.1633008