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BMC Nephrol. 2025 Jul 1;26(1):295. doi: 10.1186/s12882-025-04245-6.

ABSTRACT

BACKGROUND: Myocardial infarction is a major cause of morbidity and mortality, often leading to heart and kidney dysfunction. Despite advancements in treatment, the link between heart and kidney damage is poorly understood. This study aims to evaluate the potential protective effect of Carvacrol, a natural bioactive compound, on kidney injury induced by myocardial infarction.

METHODS: In this experimental study, 32 male Wistar rats were divided into four groups: Control, Carvacrol (50 mg/kg), Myocardial Infarction (85 mg/kg isoproterenol), and Myocardial Infarction + Carvacrol (50 mg/kg Carvacrol + 85 mg/kg isoproterenol). Carvacrol was administered for six weeks, and myocardial infarction was induced with isoproterenol. Blood pressure, biochemical parametres (creatinin kinase, lactate dehydrogenase, urea, creatinine, GDF-15, IL-6), and kidney tissue histopathology were evaluated.

RESULTS: Biochemical analysis showed increased Creatinin Kinase and Lactate Dehydrogenase levels in the Myocardial Infarction group compared to controls(p = 0.023, p = 0.020), with carvacrol reducing these markers. IL-6 and GDF-15 levels were elevated in both the Myocardial Infarction and Myocardial Infarction + Carvacrol groups (p = 0.009, p < 0.001). Blood pressure was significantly reduced in the Myocardial Infarction group. Histopathological examination revealed severe kidney damage in the Myocardial Infarction group, while Carvacrol treatment showed less kidney damage, with only mild tubular dilation and rare necrosis.

CONCLUSION: Carvacrol appears to have protective effects against kidney injury in myocardial infarction. It reduced myocardial injury markers and kidney damage, suggesting its potential therapeutic use in cardiorenal syndrome. Further studies are needed to understand its mechanisms and clinical applications in cardiovascular and renal diseases.

PMID:40597757 | DOI:10.1186/s12882-025-04245-6

Sci Rep. 2025 Jul 1;15(1):21563. doi: 10.1038/s41598-025-08099-8.

ABSTRACT

Ranolazine is known for its antiarrhythmic, antianginal, anti-ischemic properties, as well as its favorable effects on glycemic control. This study aimed to evaluate the effects of ranolazine on oxidative-antioxidative balance and angiogenesis using an in vivo experimental model. A total of 40 Ross 308 chick embryos were used and randomly divided into four groups (n = 10 per group). On the eighth day of incubation, vascular density was assessed. Following vascular evaluation, 4-5 mL of albumen was aspirated using a syringe to measure oxidative stress markers. The groups were as follows: Control, Bevacizumab (BC), Ranolazine 10-4, and Ranolazine 10-5. Total antioxidant capacity (TAC) levels were significantly higher in the bevacizumab group compared to the control group (p < 0.05). Similarly, oxidative stress index (OSI) levels were also significantly elevated in the bevacizumab group (p < 0.05). Both Ranolazine 10-4 and 10-5 groups demonstrated significantly increased TAC levels compared to the control group (p < 0.05). In terms of angiogenesis scores, bevacizumab exhibited a marked anti-angiogenic effect compared to control. However, no statistically significant difference was observed between the ranolazine groups and the control group regarding angiogenesis scores (p > 0.05). This study provides the first in vivo evidence that Ranolazine enhances total antioxidant capacity but does not influence angiogenesis in the CAM model. Future research should explore the molecular mechanisms underlying this effect.

PMID:40596615 | PMC:PMC12215869 | DOI:10.1038/s41598-025-08099-8

Sci Rep. 2025 Jul 1;15(1):20725. doi: 10.1038/s41598-025-07576-4.

ABSTRACT

Doxorubicin (DOX) is an effective anticancer drug, but its clinical application is limited due to its severe adverse effects on multiple organs and tissues, particularly cardiotoxicity. Studies suggest that metformin and Coenzyme Q10 (CoQ10) may help reduce DOX-induced cardiotoxicity. This study investigated the individual and combined effects of metformin and CoQ10 on DOX-induced cardiotoxicity in rats. 36 male Wistar rats were divided into six groups consisting of N_C, C_Dox (25 mg/kg DOX), C_(Met + Q10) (200 mg/kg metformin + 10 mg/kg CoQ10), T_Met (200 mg/kg metformin + 25 mg/kg DOX), T_Q10 (10 mg/kg CoQ10 + 25 mg/kg DOX), and T_(Met + Q10) (200 mg/kg metformin + 10 mg/kg CoQ10 + 25 mg/kg DOX). DOX administration significantly elevated serum CK-MB, LDH (P < 0.05), and tissue MDA (P < 0.001). It also significantly decreased TAC, CAT, GPx (P < 0.001), and SOD (P < 0.01) in heart tissues. Treatment with metformin and CoQ10 significantly restored the biochemical parameters both in the serum and tissue samples and ameliorated the histopathological damage caused by DOX. In conclusion, the combination of metformin and CoQ10 exerted antioxidant and cardioprotective effects against DOX-induced cardiotoxicity.

PMID:40596564 | PMC:PMC12214982 | DOI:10.1038/s41598-025-07576-4

Sci Rep. 2025 Jul 1;15(1):20859. doi: 10.1038/s41598-025-08720-w.

ABSTRACT

Myocardial infarction is a leading cause of death and morbidity in individuals with cardiovascular diseases. Natural antioxidants, such as those found in green tea leaves, are beneficial in preventing these diseases. This study evaluated the protective effects of green tea leaves powder against isoprenaline (ISO)-induced myocardial infarction in rats. Four groups of male Long Evans rats were used: Control, Control + green tea leaves powder, ISO, and ISO + green tea leaves powder. Organ and blood plasma samples were collected to measure oxidative stress biomarkers, biochemical parameters, and gene expressions. Furthermore, tissue sections were prepared and stained histologically. ISO-induced rats showed decreased cellular antioxidants (catalase activity and glutathione concentration) and elevated oxidative stress markers. Notable inflammatory cell infiltration and fibrosis were observed in the heart and kidneys of ISO-induced rats. Supplementation with green tea leaves powder significantly restored catalase activity and glutathione concentration (p < 0.05) in plasma and tissues. It also considerably reduced lipid peroxidation, nitric oxide, and advanced oxidation protein products (p < 0.05) in ISO-administered rats. Furthermore, green tea leaves powder supplementation halted inflammatory gene expression (p < 0.05), restored antioxidant genes (p < 0.05) such as Nrf-2-HO-1, and prevented cardiac fibrosis in ISO-administered rats. Green tea leaves powder supplementation may reduce oxidative stress, inflammation, and fibrosis in ISO-administered rats, potentially through the Nrf-2-HO-1-mediated restoration of antioxidant enzymes and prevention of heart inflammation.

PMID:40596364 | DOI:10.1038/s41598-025-08720-w

Sci Rep. 2025 Jul 1;15(1):22067. doi: 10.1038/s41598-025-03419-4.

ABSTRACT

Doxorubicin (DOX) is an anthracycline class of chemotherapy drug, the application of which is limited due to its cardiotoxic effects. Recombinant Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), is a serine protease pivotal in lipid metabolism and has a profound correlation with the onset of cardiovascular diseases. This study uncovers a connection between PCSK9 and DOX-induced cardiotoxicity (DIC). This research found that injection of DOX in mice caused cardiac toxicity. DOX treatment up-regulated the expression of PCSK9 protein in myocardial tissue. Evolocumab (PCSK9 inhibitors) improved cardiac function, myocardial injury, and fibrosis in DOX-treated mice, indicating a protective effect against DIC. The mechanism involved modulation of cardiomyocyte apoptosis and regulation of apoptosis-related proteins, including Bax/Bcl-2 ratio and Cleaved Caspase-3/Pro Caspase-3 ratio. DOX exhibited concentration- and time-dependent cytotoxic effects on H9C2 cardiomyocytes, promoting apoptosis. PCSK9 nuclear aggregation occurred in H9C2 cardiomyocytes after DOX treatment, and PCSK9 interacted with the Importin subunit beta-1 (KPNB1) protein. Interference with PCSK9 up-regulated KPNB1 expression, affecting apoptosis-related proteins and improving DOX-induced H9C2 cardiomyocyte apoptosis. In short, the elucidation of this mechanism is helpful involve that PCSK9 inhibitor may be a potential drug for improving DIC.

PMID:40593844 | PMC:PMC12215775 | DOI:10.1038/s41598-025-03419-4

Nat Commun. 2025 Jul 1;16(1):5927. doi: 10.1038/s41467-025-61028-1.

ABSTRACT

Cardiac hypertrophy leads to ventricular dysfunction and heart failure. Deubiquitinating enzymes are responsible for preserving the substrate protein stability and are essential to myocardial hypertrophy. In this study, we aimed to explore the role and regulatory mechanism of a cardiomyocyte-derived deubiquitinating enzyme, USP13, in cardiac hypertrophy. Here we show that USP13 was increased in hypertrophic myocardium and was mainly distributed in cardiomyocytes. Cardiomyocyte-specific Usp13 knockout aggravated TAC or Ang II-induced myocardial hypertrophy and dysfunction in male mice. Correspondingly, USP13 overexpression by AAV9 in hearts exerted a therapeutic impact on cardiac hypertrophy in male mice. Mechanistically, we identified STAT1 as a substrate of USP13 through interactome analysis. USP13 deubiquitinated STAT1, thereby reducing its degradation. Subsequently, USP13 promoted the STAT1-targeted Nppb gene transcription and enhanced mitochondrial function in cardiomyocytes. This study illustrated a beneficial effect of USP13 in hypertrophic cardiomyocytes and identified a cardiomyocyte-specific USP13-STAT1 axis in regulating cardiac hypertrophy.

PMID:40593642 | PMC:PMC12217623 | DOI:10.1038/s41467-025-61028-1

JHLT Open. 2025 May 29;9:100282. doi: 10.1016/j.jhlto.2025.100282. eCollection 2025 Aug.

ABSTRACT

The Fontan population has increased dramatically owing to advances in medical and surgical therapies, with many living well into adulthood with Fontan circulation. Unfortunately, patients will develop heart failure due to the chronic effects of their altered circulatory system. Management of heart failure in these patients is very complex and requires multi-disciplinary approaches with input from both cardiologists and surgeons. In the case of patients who develop cardiogenic shock, transplantation is often not feasible due to instability. Recently, there has been increased use of ventricular assist devices (VADs) as a bridge to transplantation with promising results. In this work, we briefly review the physiology of Fontan failure, provide criteria for VAD workup, and discuss VAD outcomes in Fontan patients. Finally, we describe a single institution's experience and outcomes with VADs in Fontan patients.

PMID:40599905 | PMC:PMC12209974 | DOI:10.1016/j.jhlto.2025.100282

Acta Clin Croat. 2024 Mar;63(Suppl1):14-17. doi: 10.20471/acc.2024.63.s1.2.

ABSTRACT

Cardiac allograft vasculopathy (CAV) is diffuse concentric narrowing caused by intimal fibriproliferation of the coronary arteries in patients after heart transplantation (HTx). It affects almost one third of patients over the period of 5 years, and more than 50% after 10 years following HTx and remains a common cause of late graft failure and mortality. Percutaneous coronary intervention (PCI) can be attempted for focal disease preferably with drug-eluting stents, but the only definite solution is re-transplantation reserved for selected patients with severe CAV. We report a case of a 33- year-old patient with a newly diagnosed CAV, in which a PCI of circumflex coronary artery was attempted, resulting in a coronary perforation treated by the placement of a covered single stent.

PMID:40599471 | PMC:PMC12207855 | DOI:10.20471/acc.2024.63.s1.2

J Med Life. 2025 May;18(5):428-439. doi: 10.25122/jml-2025-0061.

ABSTRACT

Patients with cancer and severe COVID-19 pneumonia treated with injectable azithromycin and anakinra frequently develop dysglycemia, necessitating initiation of sulfonylurea therapy (gliquidone or glimepiride). We retrospectively reviewed adults (≥30 years) with diabetes and cancer who were hospitalised for COVID-19 at the Central Military Hospital Bucharest and the Matei Bals National Institute between March 2020 and August 2022. All patients completed a 14-day course of azithromycin + anakinra and survived to discharge. Glycaemic control was achieved with fixed-dose gliquidone 30 mg or glimepiride 2, 3, or 6 mg, chosen according to each patient's inflammatory-cardiac profile. Central insulin resistance may lead to the risk of cardiometabolic syndrome through the increase of inflammatory markers (TNF-alpha and PAI-1), treated with gliquidone, in 50 patients with cancer infected with COVID-19, who were dependent on developing immunothrombosis. Peripheral insulin resistance leads to the risk of cardiovascular events through the increase of inflammatory markers, IL-6 and Il-1, treated with glimepiride, in 50 patients with cancer infected with COVID-19.

PMID:40599143 | PMC:PMC12207693 | DOI:10.25122/jml-2025-0061

World J Pediatr Congenit Heart Surg. 2025 Jul 2:21501351251347948. doi: 10.1177/21501351251347948. Online ahead of print.

ABSTRACT

Temporary mechanical circulatory support (tMCS) has been utilized as a bridge to heart transplantation with increasing duration of support. We describe the clinical course of a 14-year-old patient, with TNNT2 and KCNQ1 mutations, requiring Impella 5.5 support for 76 days. We discuss the patient's underlying genetic etiology, potential complications of prolonged tMCS, and the importance of multidisciplinary support. To our knowledge, this is the first published case in which a patient has this specific combination of genetic mutations and the longest published support duration of an Impella 5.5 in a pediatric patient.

PMID:40598957 | DOI:10.1177/21501351251347948

Adv Sci (Weinh). 2025 Jul 1:e06968. doi: 10.1002/advs.202506968. Online ahead of print.

ABSTRACT

Supercooling preservation holds great promise for extending the storage limits of organs. However, supercooled systems are susceptible to stochastic ice nucleation, which can cause fatal damage to the organs. In this study, an organogel interface composed of nanoscale polydimethylsiloxane and dimethyl-silicone oil is proposed, which presents a significant energy barrier for ice nucleation, comparable to that of homogeneous nucleation. The organogel effectively eliminates primary ice nucleation sites, enabling a quasi-homogeneous supercooling preservation system that does not rely on cryoprotectant agents or machine perfusion. Through a series of statistical experiments, this approach is demonstrated to be able to maintain stable supercooling and preserve mouse hearts at -4 °C for up to 72 h. A comprehensive assessment conducted at multiple scales indicates that the 36-h supercooling preservation at -4 °C significantly mitigates cardiac injury by regulating mitochondrial structure and reducing metabolic rates. Utilizing a heart transplantation model with prognostic evaluations extending up to 3 months post-transplantation, supercooling preservation within the quasi-homogeneous system is confirmed, which can double the storage duration compared to clinically applied hypothermic preservation methods.

PMID:40598840 | DOI:10.1002/advs.202506968

BMC Nutr. 2025 Jul 2;11(1):116. doi: 10.1186/s40795-025-01094-2.

ABSTRACT

BACKGROUND/AIM: We conducted the Mendelian Randomization (MR) analysis to investigate the causal relationship between serum saturated fatty acids (SFAs) and the risk of heart stroke (HS).

METHODS: The MRC-IEU Consortium provided summary statistics datasets related to SFAs, encompassing 64,979 individuals of European descent. Genetic variants associated with HF were identified using a GWAS dataset comprising 461,880 participants (cases = 7,055, controls = 454,825) of European descent from the UK Biobank. Generalized summary Mendelian Randomization (GSMR) assessed the potential association. Additionally, we performed a two-sample Mendelian Randomization (TSMR). The odds ratio (OR) with 95% confidence intervals (CIs) was indicated.

RESULTS: The GSMR results suggested no significant between SFA and HS [OR = 1.002, 95% CI: 0.995, 1.009; P-value = 0.752]. TSMR revealed [ORIVW = 1.005, 95% CI: 0.998, 1.012; P-value = 0.169]. MR Egger (Q = 6.14, Q_pvalue = 0.292), IVW (Q = 6.24, Q_pvalue = 0.396; I2 = 18.7%) for heterogeneity test, and Egger intercept = 1.14 × e-4, p-value = 0.792 for pleiotropy test were performed. These findings remained consistent across various Mendelian Randomization methods, including IVW [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.169], Simple median [OR = 1.009, 95% CI: 0.99-1.02, p-value = 0.08], MR-Egger [OR = 1.001, 95% CI: 0.97-1.03, p-value = 0.97], Robust Adjusted Profile Score [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.167], MR-Lasso [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.169], Constrained maximum likelihood (MR-cML) [OR = 1.006, 95% CI: 0.99-1.01, p-value = 0.168], Weighted mode [OR = 1.01, 95% CI: 0.99-1.02, p-value = 0.279], Maximum-likelihood method [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.158].

CONCLUSION: Our MR study did not yield convincing evidence supporting the association of SFAs with HF risk. Future studies should focus on alternative approaches to investigate this association.

PMID:40598686 | PMC:PMC12218826 | DOI:10.1186/s40795-025-01094-2

J Med Case Rep. 2025 Jul 1;19(1):304. doi: 10.1186/s13256-025-05359-z.

ABSTRACT

BACKGROUND: Nocardia species are opportunistic pathogens typically transmitted through inhalation or direct skin contact, causing various clinical manifestations, particularly in immunocompromised individuals. Nocardia spp. infection with severe clinical manifestations is rare in immunocompetent patients. In immunocompetent patients, complicated clinical presentations-central nervous system involvement, including multiple large and encapsulated brain abscesses with vasogenic edema and countless miliary-like lesions involving the brain, cerebellum, and brain stem-are rare, and treatment with plain antibiotic therapy to complete remission is highly unlikely compared with the emphasized combined neurosurgical interventions.

CASE PRESENTATION: We presented the case of a 67-year-old Iranian male with Nocardia spp. infection, an immunocompetent patient with prolonged and insidious manifestation that involved lung and central nervous system with solitary mature and countless miliary-like brain abscesses. Treatment with high-dose parenteral trimethoprim-sulfamethoxazole and meropenem for 6 weeks, followed by oral trimethoprim-sulfamethoxazole, successfully managed the disease without requiring neurosurgical intervention despite clinical indications. A follow-up brain magnetic resonance imaging showed that treatment led to the shrinkage of brain lesions.

CONCLUSION: We presented a case of Nocardia spp.-infection spp. infection in an immunocompetent patient with no significant history or comorbidities. The patient presented with a central nervous system infection characterized by solitary and miliary-like lesions. This case highlights the importance of considering Nocardia spp. infection as a differential diagnosis, particularly in patients with insidious and complex clinical manifestations. Meanwhile, it seems that more precise neurosurgical indications are necessary.

PMID:40598635 | PMC:PMC12220760 | DOI:10.1186/s13256-025-05359-z

J Transl Med. 2025 Jul 1;23(1):710. doi: 10.1186/s12967-025-06772-0.

ABSTRACT

Heart transplantation (HTx) remains the definitive treatment for patients with end-stage heart disease. Despite the number of HTx performed annually in worldwide continues to increase, complications of HTx still impact the quality of life and long-term prognosis, including rejection, infection, and allograft dysfunction. Endomyocardial biopsy remains the gold standard for monitoring cardiac allograft rejection post-heart transplantation, yet its invasiveness and interobserver error in histologic grading necessitate the development of novel noninvasive biomarkers to elucidate rejection mechanisms and progression. Cardiac allograft vasculopathy, a critical determinant of long-term outcomes, is challenging to detect early via intravascular ultrasound, underscoring the potential of plasma biomarkers for disease surveillance. Omic technologies usually refers to the application of multiple high-throughput screening technologies enabling comprehensive analysis of biological systems at a molecular level. Multi-omics technologies, including genomics(donor-derived cell-free DNA), transcriptomics(microRNAs panels, gene expression profiling), proteomics(cell signaling molecule), and metabolomics(ex situ heart perfusion), have demonstrated significant promise in post-transplant monitoring. These approaches provide personalized risk stratification and mechanical insights into cardiac allograft rejection, primary graft dysfunction, and cardiac allograft vasculopathy. Single-cell omics technologies and machine learning algorithms further resolve cellular heterogeneity and improve predictive modeling, thereby enhancing the clinical translatability of multi-omics data. This comprehensive review synthesizes these advances and highlights the transformative potential of integrating multi-omics with advanced analytics to achieve precision monitoring and therapy in HTx, ultimately improving long-term patient outcomes.

PMID:40598485 | DOI:10.1186/s12967-025-06772-0

Sci Rep. 2025 Jul 1;15(1):21174. doi: 10.1038/s41598-025-07317-7.

ABSTRACT

Recovery and clinical outcomes following organ transplantation may be negatively influenced by psychological distress. Limited reports from recipients indicate that thoughts and feelings related to the donor/transplanted organ - referred to as donor and donation images (DDI) - may be a source of such distress. The term DDI encompasses all thoughts and emotions that organ recipients associate with the donor or the donated organ. However, empirical knowledge of DDI remains limited. This quantitative survey involving 407 participants represents the first and largest study to quantitatively examine DDI in patients after heart transplantation (HTX). The results revealed a very high prevalence of DDI (91%), with occurrences reported intermittently and often clustered around the time of transplantation, both before and after HTX. Psychological distress predicted the occurrence of DDI before and after HTX and almost all emotions experienced and reported pre-HTX were associated with higher odds of pre-HTX DDI, suggesting it may be a concurrent phenomenon of overall emotional activation. Due to the involvement of emotions associated with uncertainty and low personal control, along with high situational control, DDI may be a part of coping. Some reported avoiding DDI suggesting that, sometimes, they might also represent a stressor. Future studies should further investigate the effects of DDI, including its impact on transplant outcome.

PMID:40596616 | PMC:PMC12219023 | DOI:10.1038/s41598-025-07317-7

Sci Rep. 2025 Jul 1;15(1):21214. doi: 10.1038/s41598-025-04405-6.

ABSTRACT

The efficacy of stem cell therapy for ischemic stroke in terms of functional outcomes remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (PROSPERO: CRD42024503763) to assess the efficacy and safety of stem cell therapy for acute/subacute ischemic stroke, focusing on long-term outcomes. Studies of patients undergoing stem cell transplantation within 1 month of stroke onset were included. We searched five databases for publications up to January 17, 2024. Summary data were extracted from published reports. The primary outcome was the modified Rankin Scale (mRS) score. Measures of effect were risk ratios (RRs) with 95% confidence intervals (CIs). A random-effects model was used when I2 was > 25%; otherwise, a fixed-effects model was used. Common serious adverse events were epilepsy, gastrointestinal disorders, and cardiac disorders. The risk of bias was assessed using the Cochrane Risk of Bias tool version 2. In total, 13 trials involving 872 (519 men) patients were included. The 1-year incidence of mRS scores 0-1 was higher in the cell-therapy group (45/195) than that in the control group (23/179; RR = 1.74 [95% CI = 1.09-2.77]; p = 0.020; I2 = 0%). The 90-day incidence of mRS scores 0-2 was also higher (RR = 1.31 [95% CI = 1.01-1.70]; p = 0.044; I2 = 0%). No significant differences were observed in serious adverse events or mortality. Stem cell therapy for acute/subacute ischemic stroke within 1 month of onset is safe and significantly improves long-term functional outcomes, although the mechanisms of action need to be elucidated and treatment protocols standardized to establish stem cell therapy as a standard care option for ischemic stroke.

PMID:40595869 | PMC:PMC12217828 | DOI:10.1038/s41598-025-04405-6

Transl Psychiatry. 2025 Jul 1;15(1):217. doi: 10.1038/s41398-025-03430-3.

ABSTRACT

INTRODUCTION: Major depressive disorder (MDD) is a heterogeneous psychiatric disorder that is a risk factor for cardiovascular diseases. Autonomic dysregulation, estimated as an important correlated pathophysiological cause, was investigated in many studies mainly through a quantitative evaluation of the heart rate variability (HRV).

AIM: The objective of this review was to provide any reproducible insights on autonomic regulation characteristics of MDD through the selection, revision, and joint interpretation of a restricted sample of studies based on systematic criteria.

METHODS: The literature research resulted in thirty eligible articles that reported the comparison of short-term resting-state HRV measures between drug-free MDD patients and healthy controls, excluding subjects affected by cardiovascular diseases.

RESULTS: Most of the reviewed studies reported significant differences between MDD patients and controls in the investigated HRV measures, especially for those that mainly reflect vagal activity. Nonlinear measures, although computed by fewer studies, seem to be more sensitive in detecting autonomic changes in MDD.

CONCLUSIONS: Our findings can be considered as evidence that the intrinsic autonomic state of MDD is characterized by decreased parasympathetic tone, which, interpreted in the context of the polyvagal theory, might be associated with impaired emotion regulation and flexible adjustment in MDD.

PMID:40595479 | PMC:PMC12215732 | DOI:10.1038/s41398-025-03430-3

Commun Med (Lond). 2025 Jul 1;5(1):266. doi: 10.1038/s43856-025-00963-y.

ABSTRACT

BACKGROUND: Cell therapy, particularly using cardiomyocytes, shows significant promise for treating heart failure. Direct reprogramming of somatic cells into cardiomyocytes using small molecules is advantageous due to its efficiency and cost-effectiveness.

METHODS: Human urine-derived cells (hUCs) were transdifferentiated into functional cardiomyocyte-like cells (hCiCMs) using a cocktail of 15 small molecules under xeno-free conditions. Various Characterizations were performed, including immunofluorescence, transmission electron microscopy (TEM), qPCR, single-cell RNA sequencing, patch-clamp recordings, and intracellular Ca²+ measurements. The therapeutic potential was tested in both mouse and porcine models of myocardial infarction (MI).

RESULTS: Reprogramming efficiency achieves 15.08% on day 30, with purity reaching 96.67% on day 60. hCiCMs display cardiomyocyte markers, sarcomeric structures, and abundant mitochondria. Electrophysiological analysis confirms ventricular-like action potentials and regular calcium transients. Single-cell RNA sequencing reveals cardiomyocyte subpopulations resembling 13-week embryonic human heart cells, with gene ontology analysis indicating successful maturation. In the MI model, hCiCM transplantation improves cardiac function, increasing ejection fraction and fractional shortening while reducing fibrosis.

CONCLUSIONS: This study demonstrates the successful reprogramming of hUCs into functional hCiCMs using small molecules under xeno-free conditions, offering a scalable, autologous cell source for cardiac repair with significant potential for regenerative therapies.

PMID:40595290 | PMC:PMC12216017 | DOI:10.1038/s43856-025-00963-y

Sci Rep. 2025 Jul 1;15(1):22327. doi: 10.1038/s41598-025-08315-5.

ABSTRACT

The interactions between CD40 and tumor necrosis factor receptor-associated factor 6 (TRAF6) are implicated in chronic inflammation and fibrosis. Given their poorly understood role in chronic transplant rejection, our study focused on investigating the CD40-TRAF6 interactions in murine models of cardiac transplantation, particularly in relation to cardiac allograft vasculopathy (CAV). We established murine heart transplantation models using BALB/C to C57BL/6 and H-2bm12 to C57BL/6 pairings. A specific antagonist for TRAF6 was administered post-transplantation, either alone or in combination with cyclosporin A (CsA). We analyzed cells infiltrating the cardiac allografts and splenic immune cells. Additionally, We explore the potential mechanistic effects of TRAF6 inhibition in CAV by bone marrow-derived macrophages (BMDMs) co-culture. The inhibition of CD40-TRAF6 interaction significantly prolonged the survival of cardiac allografts. When combined with CsA, this treatment induced long-term survival of the allografts. Specifically, in the H-2bm12 to C57BL/6 heart transplantation model, inhibiting TRAF6 mitigated the development of CAV. This blockade led to a decrease in CD11b + and CD4 + cells within the allografts. In vitro experiments showed that TRAF6 inhibition had limited effects on mixed lymphocyte culture responses and minimally affected the proliferation of naive CD4 + cells activated by CD3/CD28. Furthermore, BMDMs under CD40-TRAF6 inhibition were more likely to differentiate into an anti-inflammatory phenotype, and their migration capability was reduced. Our findings demonstrate that inhibiting the TRAF6 pathway can significantly ameliorate both acute and chronic allograft rejection. The combination with CsA appears to have a synergistic effect, suggesting that targeting the TRAF6 could be a beneficial co-strategy for managing alloimmune responses. Importantly, our results position TRAF6 as a promising complementary target for enhancing outcomes in CAV.

PMID:40595221 | DOI:10.1038/s41598-025-08315-5

Sci Rep. 2025 Jul 1;15(1):20573. doi: 10.1038/s41598-025-06607-4.

ABSTRACT

This study was aimed at developing and internally validating nomograms for predicting mortality during venoarterial-extracorporeal membrane oxygenation (VA-ECMO) and in-hospital mortality risk in patients treated with VA-ECMO. A total of 7260 patients treated with VA-ECMO from January 2017 to December 2023 were extracted from the Chinese society of extra corporeal life support registry database. The entire cohort was randomly assigned to derivation and validation cohorts at a ratio of 2:1. Multivariable Cox proportional hazards regression was conducted using bootstrapping with the likelihood ratio test and Akaike information criterion. Approximately 24% of patients died during VA-ECMO assistance, and 51% died in the hospital. The nomogram PROFIT was constructed with ten pre- and immediately post-ECMO parameters: age, body mass index (BMI), intra-aortic balloon pump before VA-ECMO, history of cardiac arrest, worst mean arterial pressure (MAP), potential of hydrogen (pH) and serum lactate levels before VA-ECMO, site of ECMO installation, peripheral cannulation and distal perfusion. Additionally, nomogram POSITIVE was also established with ten parameters: age, sex, BMI, history of cardiac arrest, MAP, pH, and serum lactate levels before VA-ECMO support, the occurrence of cardiac arrest before VA-ECMO, type of sedation and prior continuous renal replacement therapy. The area under the receiver operating characteristics (AUC) of the nomogram PROFIT (0.72 [95% CI 0.70-0.74]) and POSITIVE (0.71 [95% CI 0.68-0.73]) outperformed the SAVE score, which indicated that the nomograms were capable of effectively identifying patients with a high risk of mortality. Both nomograms demonstrated outstanding discrimination and calibration in derivation and validation cohorts. In patients treated with VA-ECMO, the nomogram PROFIT may serve as a valuable tool for predicting mortality during VA-ECMO assistance, and the nomogram POSITIVE can predict in-hospital mortality with high reliability. However, these tools still require external validation in other patient populations requiring VA-ECMO support.

PMID:40594967 | PMC:PMC12215877 | DOI:10.1038/s41598-025-06607-4