Agregador de feeds

Ann Intensive Care. 2025 May 6;15(1):61. doi: 10.1186/s13613-025-01462-y.

ABSTRACT

BACKGROUND: This post-hoc analysis of a multinational, multicenter study aimed to describe and compare clinical characteristics, microbiology, and outcomes between immunosuppressed and non-immunosuppressed patients with nosocomial lower respiratory tract infections (nLRTI). The study utilized data from the European Network for ICU-related Respiratory Infections, including 1,060 adult ICU patients diagnosed with nLRTI. Descriptive statistics were used to compare baseline characteristics and pathogen distribution between groups. A Cox proportional hazards model stratified by immunosuppression status was applied to assess 28-day mortality risk, adjusting for disease severity and key clinical variables.

RESULTS: Immunosuppression was observed in 24.9% (264/1060) of the patients, and oncological conditions were the most common etiology of immunosuppression. Chronic pulmonary and cardiovascular diseases were the most frequent comorbidities. In both groups, Pseudomonas aeruginosa was the predominant microorganism, particularly affecting patients with immunosuppression (25.3% vs. 16.7%, p = 0.032). Cox regression model adjusted for disease severity (SAPS II), polytraumatized status, altered consciousness, and postoperative status, SAPS II remained a strong independent predictor of mortality, with each one-point increase associated with a 2.3% higher risk of death (HR: 1.023, 95% CI 1.017-1.030, p < 0.001). The analysis also revealed significant heterogeneity in mortality risk among immunosuppressed patients, with hematological malignancies, recent chemotherapy, and bone marrow transplantation associated with the highest mortality.

CONCLUSIONS: Immunosuppressed patients had a lower adjusted survival probability compared to non-immunosuppressed patients. Moreover, P. aeruginosa was the most frequently identified etiological pathogen in immunosuppressed patients.

PMID:40328994 | PMC:PMC12055687 | DOI:10.1186/s13613-025-01462-y

Stem Cell Rev Rep. 2025 May 5. doi: 10.1007/s12015-025-10888-7. Online ahead of print.

ABSTRACT

This review examines the application of stem cell therapy in myocardial remodeling following myocardial infarction, delving into the complex changes in the cardiac microenvironment after myocardial infarction, the potential mechanisms of stem cell treatment, and the progress of clinical research. It also provides an outlook on future research directions and clinical applications. After myocardial infarction, the heart undergoes a series of complex biological processes, including cardiomyocyte death and hypertrophy, activation and transdifferentiation of fibroblasts, remodeling of the extracellular matrix, functional changes in endothelial cells, and activation of inflammatory responses. These processes ultimately lead to pathological alterations in cardiac structure and function, known as cardiac remodeling. Stem cell therapy and its cell derivatives improve cardiac structure and function through multiple pathways, such as inducing myocardial regeneration, promoting angiogenesis, modulating the inflammatory microenvironment, and reducing fibrosis. However, stem cell therapy still faces many challenges in the treatment of myocardial infarction, such as low cell survival rates, excessive fibrosis, and low clinical translation efficiency. Despite these challenges, stem cell therapy, as an emerging treatment modality, shows great potential in cardiac remodeling after myocardial infarction. Therefore, this article, through its outlook on future research directions, emphasizes the importance of optimizing treatment strategies, developing new technologies, and conducting multicenter clinical trials, providing theoretical basis and practical guidance for the clinical application of stem cell therapy in myocardial repair after myocardial infarction.

PMID:40323498 | DOI:10.1007/s12015-025-10888-7

Turk Gogus Kalp Damar Cerrahisi Derg. 2024 Dec 31;32(4 Suppl 2):068-68. doi: 10.5606/tgkdc.dergisi.2024.msb-43. eCollection 2024 Nov.

ABSTRACT

OBJECTIVE: This study aimed to share the early results of the pulmonary endarterectomy program recently implemented in our clinic in the treatment of chronic thromboembolic pulmonary hypertension.

METHODS: Eighteen patients (10 females, 8 males; mean age: 46 years) who underwent pulmonary endarterectomy between October 2022 and August 2024 were included in the retrospective study. Perioperative and follow-up data, including age, in-hospital mortality, and the length of intensive care unit and hospital stays after pulmonary endarterectomy, were evaluated.

RESULTS: The majority of the patients (n=16) were New York Heart Association class III or IV before surgery. According to the University of California, San Diego level classification, almost all patients had at least level 1 and 2 lesions in one or more pulmonary artery (n=17). Cardiopulmonary bypass time, cross-clamp time, and total circulatory arrest time were 174.8±16.6, 34.7±12.2, and 21,7±6.2 min, respectively. The in-hospital mortality rate was 5.5% (n=1), and the morbidity rate was 16.6% (n=3). Extracorporeal membrane oxygenation was performed on two patients (one venoarterial, one venovenous). Both patients were successfully weaned off ECMO. However, the patient who received venoarterial ECMO died due to multiorgan failure in the second postoperative month. After pulmonary endarterectomy, the durations of mechanical ventilation, intensive care stay, and hospital stay before discharge were 6.1±13.1, 17.8±14.7, and 20.01±13.9 days, respectively. The systolic and mean pulmonary artery pressure fell from 97.6±22.6 and 63.1±18.1 mmHg before surgery to 42.5±12.8 and 25.7±6.1 mmHg after surgery.

CONCLUSION: Pulmonary endarterectomy is a highly effective treatment for chronic thromboembolic pulmonary hypertension, providing dramatic clinical improvement in the early term with acceptable mortality and morbidity rates.

PMID:40322154 | PMC:PMC12045168 | DOI:10.5606/tgkdc.dergisi.2024.msb-43

Anaesth Crit Care Pain Med. 2025 Apr 30;44(4):101539. doi: 10.1016/j.accpm.2025.101539. Online ahead of print.

NO ABSTRACT

PMID:40315993 | DOI:10.1016/j.accpm.2025.101539

Diagnostics (Basel). 2025 Apr 10;15(8):961. doi: 10.3390/diagnostics15080961.

ABSTRACT

Background/Objectives: Myocarditis is a major cause of morbidity and mortality in children and can lead to long-term heart failure, dilated cardiomyopathy, the need for heart transplantation, or death. New systemic inflammatory indices that combine lymphocyte, neutrophil, and platelet counts have been recently used as strong prognostic markers of some inflammatory diseases and adverse outcomes of neoplasms. This study aimed to investigate the use of new systemic indices as early predictive markers for adverse outcomes in patients with pediatric myocarditis. Methods: This study retrospectively examined patients between the ages of >1 month and <18 years who were monitored in our clinic with a diagnosis of myocarditis between 1 January 2022 and 31 December 2024. The cases were divided into two groups: fulminant myocarditis (requiring the use of inotropes or extracorporeal membrane oxygenation due to hemodynamic disturbance) and non-fulminant myocarditis. The systemic inflammatory index values of these groups (calculated in the first 6 h) were compared, and the results were statistically analyzed. Results: The study included 122 pediatric myocarditis cases treated during the study period (80 boys; median age: 11 (IQR: 8-14) years). Twenty-six of these patients (21.3%) developed fulminant myocarditis. The median systemic immune-inflammation index (SII) value in the group with fulminant myocarditis was 1300 (IQR: 1000-1600), while this value was 500 (IQR: 350-650) for the non-fulminant group (p < 0.05). The median systemic inflammatory response index (SIRI) values were 2.9 (IQR: 2.5-3.2) in the fulminant myocarditis group and 1.5 (IQR: 1.2-1.8) in the non-fulminant group (p < 0.05). The cut-off values for fulminant myocarditis were found to be 1050 for the SII, with an AUC value of 0.76 (95% confidence interval: 0.80-0.96; p < 0.001), and 1.9 for the SIRI, with an AUC value of 0.64. Conclusions: The SII and SIRI may independently predict adverse myocarditis prognoses in children. These new biomarkers are easy to calculate using routine blood parameters.

PMID:40310387 | PMC:PMC12025616 | DOI:10.3390/diagnostics15080961

Nat Cardiovasc Res. 2025 May;4(5):602-623. doi: 10.1038/s44161-025-00635-z. Epub 2025 Apr 29.

ABSTRACT

Elucidating the regulatory mechanisms of human cardiac aging remains a great challenge. Here, using human heart tissues from 74 individuals ranging from young (≤35 years) to old (≥65 years), we provide an overview of the histological, cellular and molecular alterations underpinning the aging of human hearts. We decoded aging-related gene expression changes at single-cell resolution and identified increased inflammation as the key event, driven by upregulation of ARID5A, an RNA-binding protein. ARID5A epi-transcriptionally regulated Mitochondrial Antiviral Signaling Protein (MAVS) mRNA stability, leading to NF-κB and TBK1 activation, amplifying aging and inflammation phenotypes. The application of gene therapy using lentiviral vectors encoding shRNA targeting ARID5A into the myocardium not only mitigated the inflammatory and aging phenotypes but also bolstered cardiac function in aged mice. Altogether, our study provides a valuable resource and advances our understanding of cardiac aging mechanisms by deciphering the ARID5A-MAVS axis in post-transcriptional regulation.

PMID:40301689 | DOI:10.1038/s44161-025-00635-z

J Clin Med. 2025 Apr 13;14(8):2662. doi: 10.3390/jcm14082662.

ABSTRACT

Background/Objectives: The impact of different coronary artery bypass grafting (CABG) strategies, particularly on-pump versus off-pump techniques, on red blood cell (RBC) transfusions and their associated outcomes has not been fully investigated. This study aims to evaluate the association between RBC transfusion and survival in CABG patients, focusing on-pump strategy. Methods: Data from CABG patients were retrieved from the National Health Insurance Service database (2003 to 2019). Perioperative RBC transfusions were classified into three groups: no transfusion, RBC 1, and RBC ≥ 2 units. The primary endpoint was all-cause mortality rate. Subgroup analysis assessed the impact of RBC transfusion on mortality across the conventional on-pump (CCAB) and off-pump (OPCAB) groups. Results: Among the 6150 participants who underwent CABG, 2028 underwent CCAB and 4122 underwent OPCAB. The mean age was 66.2 ± 9.7 years, with a mean follow-up of 2.9 (2.53-3.35) years. Multivariable analysis showed a significant association between transfusion of ≥2 RBC units and increased mortality risk (HR 2.34 [1.65-3.32], p < 0.001). Subgroup analysis showed a similar trend in both CCAB and OPCAB groups (p for interaction = 0.2). Transfusion of ≥2 units significantly increased mortality in OPCAB (HR 2.28 [1.55-3.37], p < 0.001) but not in CCAB (HR 2.96 [0.97-9.06], p = 0.057). OPCAB and surgery at large volume center was associated with a reduced risk of RBC transfusion (p < 0.01). Conclusions: Increased RBC transfusion is associated with higher long-term mortality in patients undergoing CABG. Based on a large cohort predominantly consisting of OPCAB patients, OPCAB is associated with decreased RBC transfusion requirements.

PMID:40283492 | PMC:PMC12027956 | DOI:10.3390/jcm14082662

Medicina (Kaunas). 2025 Mar 25;61(4):589. doi: 10.3390/medicina61040589.

ABSTRACT

Background and Objective: Probiotics have been shown to be effective in controlling various adverse health conditions such as antibiotic-associated diarrhea, inflammatory bowel disease, obesity, and neurological diseases. However, to our knowledge, there is no research on the preventive effect of probiotics on heart damage caused by infections. This study examined the preventive benefits of probiotics against sepsis-related heart injury using a rat model caused by lipopolysaccharide (LPS). Materials and Methods: Four groups of twenty-four male Wistar albino rats, each with six rats, were set up. For 14 days, Group 1 (Sham Group) was given oral normal saline, intraperitoneal Escherichia coli O111-B4 lipopolysaccharide (LPS Group) was given to Group 2, and oral probiotics were given to Group 3 (Probiotic Group). Escherichia coli O111-B4 lipopolysaccharide was injected intraperitoneally after Group 4 (Probiotic + LPS) received oral probiotics containing Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 (109 CFU/day). Blood samples were taken twenty-four hours following the administration of LPS. The animals were then euthanized by cervical dislocation, and samples of cardiac tissue were taken in order to assess any damage to the heart. The following serum values were measured: C-reactive protein (CRP), creatine kinase-myocardial band (CK-MB), cardiac troponin subunit I (cTn-I), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The TNF-α, IL-1β, IL-6, glutathione (GSH), malondialdehyde (MDA), Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), CRP, CK-MB, and cTn-I levels were assessed in tissue samples. Additionally, staining techniques were used to analyze histopathological alterations in tissues. Results: With the exception of serum IL-6 (p = 0.111), tissue and serum cytokine levels were considerably greater in the sepsis group (Group 2) than in the other groups (p < 0.05 to <0.001). The TAS, GSH, and SOD levels were significantly lower (p < 0.05 to <0.001) in septic rats, although the tissue levels of TOS, OSI, and MDA were significantly higher. With the exception of serum CRP in Group 3 (p = 0.328), the CK-MB, CRP, and cTn-I levels were considerably higher in Group 2 than in the other groups (p < 0.01 to <0.001). When compared to the other groups, histopathological examination showed significant alterations in the LPS group. Conclusions: Probiotics showed positive effects on oxidative stress markers and dramatically decreased sepsis-induced cardiac damage in the LPS-induced sepsis model. These results imply that probiotics could be used as a therapeutic approach to lessen the cardiac damage brought on by sepsis.

PMID:40282880 | PMC:PMC12029071 | DOI:10.3390/medicina61040589

Biochem Pharmacol. 2025 Jul;237:116955. doi: 10.1016/j.bcp.2025.116955. Epub 2025 Apr 23.

ABSTRACT

S-nitrosoglutathione (GSNO), considered vital to S-nitrosylation of proteins, has been found fundamentally important to the cardiomyocytes (CMs) maturation. Our previous studies demonstrated that GSNO treatment significantly enhanced the S-nitrosylation of 104 proteins during the differentiation of mouse embryonic stem cells (ESCs) into CMs. Mitochondrial Cx43 (mtCx43), a membrane protein implicated in the intercellular communication, also plays a pivotal role in CMs regeneration from stem cells. However, the involvement of mtCx43 S-nitrosylation in GSNO-induced myocardial differentiation has not been fully elucidated. In this study, we employed an ESCs-derived CMs differentiation model to elucidate the mechanisms underlying GSNO-induced cardiogenesis. Our findings revealed that GSNO treatment significantly up-regulated mitochondrial transmembrane potential, ATP production, reactive oxygen species (ROS) levels, respiratory chain complex Ι activity and mtCx43 hemichannel permeability in embryoid bodies (EBs). Furthermore, S-nitrosylation of mtCx43 was markedly enhanced in differentiating EBs after GSNO treatment. Overexpression of mtCx43 further amplified the pro-mitochondrial maturation effects of GSNO, whereas overexpression of a mutant form, mtCx43C271A attenuated this effect. To investigate the functional role of mtCx43 hemichannels, we pretreated EBs with Gap19, a specific mtCx43 hemichannel blocker, followed by GSNO administration. Gap19 significantly reduced in mitofusin 2 (Mfn2) expression, thereby impairing mitochondrial maturation and function. In addition, Gap19 treatment abrogated the pro-cardiogenic effects of mtCx43 S-nitrosylation. Furthermore, we demonstrated that mtCx43 S-nitrosylation-induced cardiac differentiation was dependent on mitochondrial Ca2+ uptake. In conclusion, GSNO-induced S-nitrosylation of mtCx43 enhances mitochondrial function in EBs by promoting the opening of mtCx43 hemichannels, thus facilitating the targeted differentiation of ESCs into CMs. These findings provide novel insights into the role of mtCx43 S-nitrosylation in mitochondrial regulation and cardiac lineage commitment.

PMID:40280246 | DOI:10.1016/j.bcp.2025.116955

J Funct Biomater. 2025 Apr 21;16(4):147. doi: 10.3390/jfb16040147.

ABSTRACT

The therapeutic potential of presumed cardiac progenitor cells (CPCs) in heart regeneration has garnered significant interest, yet clinical trials have revealed limited efficacy due to challenges in cell survival, retention, and expansion. Priming CPCs to survive the hostile hypoxic environment may be key to enhancing their regenerative capacity. We demonstrate that microRNA-210 (miR-210), known for its role in hypoxic adaptation, significantly improves CPC survival by inhibiting apoptosis through the downregulation of Casp8ap2, a ~40% reduction in caspase activity, and a ~90% decrease in DNA fragmentation. Contrary to the expected induction of Bnip3-dependent mitophagy by hypoxia, miR-210 did not upregulate Bnip3, indicating a distinct anti-apoptotic mechanism. Instead, miR-210 reduced markers of mitophagy and increased mitochondrial biogenesis and oxidative metabolism, suggesting a role in metabolic reprogramming. Furthermore, miR-210 enhanced the secretion of paracrine growth factors from CPCs, with a ~1.6-fold increase in the release of stem cell factor and of insulin growth factor 1, which promoted in vitro endothelial cell proliferation and cardiomyocyte survival. These findings elucidate the multifaceted role of miR-210 in CPC biology and its potential to enhance cell-based therapies for myocardial repair by promoting cell survival, metabolic adaptation, and paracrine signalling.

PMID:40278255 | PMC:PMC12028018 | DOI:10.3390/jfb16040147

ESC Heart Fail. 2025 Apr 24. doi: 10.1002/ehf2.15261. Online ahead of print.

ABSTRACT

AIMS: Cardiopulmonary bypass (CPB) is the standard approach for coronary artery bypass grafting (CABG) in advanced ischaemic cardiomyopathy. Microaxial pump support has been envisioned to allow for beating-heart CABG without CPB (MPCAB), thereby avoiding CPB-inherent complications. This study aims to compare the in-hospital and follow-up outcome of MPCAB versus CPB-CABG in patients with severely impaired left ventricular function.

METHODS AND RESULTS: Eleven patients suffering from three-vessel coronary artery disease with median ejection fraction of 27% and deemed appropriate for CABG according to a heart team decision underwent MPCAB (support up to 5.5 L/min). Propensity score matching generated a CPB-CABG control group (n = 33). The primary endpoint was defined as death from any cause by the end of the follow-up (up to 4 years). MPCAB enabled continuous intraoperative and postoperative haemodynamic stabilization and complete myocardial revascularization. After CPB-CABG, additional mechanical circulatory support was required in 45.5% (vs. 9.1% in MPCAB; P = 0.0363). The follow-up all-cause mortality after MPCAB amounted to 0% (vs. 33.3% after CPB-CABG; P = 0.0414; NNT = 3). MPCAB patients showed a significantly decreased occurrence of major adverse cardiovascular events (MACE: 0% vs. 39.4%; P = 0.0189).

CONCLUSIONS: MPCAB allows for complete surgical revascularization without the necessity of extracorporeal circulation in spite of severely impaired left ventricular function. This first comparative study on the outcome after MPCAB versus CPB-CABG demonstrates a significantly decreased risk of death as well as MACE in MPCAB patients. The MPCAB concept expands the spectrum of patients eligible for CABG without CPB towards patients with severely impaired left ventricular function.

PMID:40274291 | DOI:10.1002/ehf2.15261

Pain Ther. 2025 Jun;14(3):913-930. doi: 10.1007/s40122-025-00739-1. Epub 2025 Apr 24.

ABSTRACT

Compared with conventional sternotomy, minimally invasive cardiac surgery (MICS) is associated with significant advantages such as reduced tissue trauma, faster recovery, and shorter hospital stay. However, the management of postoperative pain caused by intercostal nerve injury, pleural irritation, and tissue retraction remains a major challenge. Despite the less invasive nature of MICS, patients often report experiencing pain similar to that experienced following conventional cardiac surgery, particularly during the acute postoperative period. Effective pain management is essential for optimizing recovery, reducing the consumption of opioids, and preventing the transition to chronic postsurgical pain. Regional anesthesia techniques play a key role in multimodal analgesia for MICS. Thoracic epidural analgesia exhibits strong analgesic efficacy; nevertheless, it remains underutilized owing to concerns regarding anticoagulation-related complications and hemodynamic instability. The thoracic paravertebral block is a safer alternative that provides comparable pain relief with fewer side effects. Similarly, ultrasound-guided fascial plane blocks, such as serratus anterior, parasternal intercostal, interpectoral + pectoserratus, and erector spinae plane blocks, have gained popularity owing to their safety and feasibility; however, the effectiveness of these blocks varies according to the surgical approach and type of incision. Systemic analgesia is an integral component of multimodal pain management in MICS. Despite the efficacy of opioids, a shift toward opioid-sparing strategies has been observed given the significant adverse effects associated with the use of opioids. Intravenous adjuncts such as dexmedetomidine, ketamine, and non-steroidal anti-inflammatory drugs can reduce opioid consumption and improve postoperative pain control. Despite advances in pain management, a single approach that can provide comprehensive analgesia for MICS remains to be established. A multimodal strategy that combines systemic and regional techniques must be developed to optimize pain management and long-term outcomes.

PMID:40272720 | PMC:PMC12085451 | DOI:10.1007/s40122-025-00739-1

Am J Cardiol. 2025 Aug 15;249:43-50. doi: 10.1016/j.amjcard.2025.04.007. Epub 2025 Apr 21.

ABSTRACT

An essential aspect of achieving early optimal outcomes in coronary artery bypass grafting (CABG) is the careful selection of conduits. Total arterial grafting (TAG) has been debated, and recent studies suggest its benefits, especially when combined with off-pump coronary artery bypass grafting (OPCAB). We conducted a systematic review and meta-analysis of studies comparing outcomes of TAG in OPCAB versus on-pump CABG (ONCAB), using data from OVID MEDLINE, EMBASE, SCOPUS, and PUBMED. Seven studies with a total of 5417 patients were included. Short-term outcomes showed no significant differences in perioperative complications between TAG-OPCAB and TAG-ONCAB, but TAG-OPCAB was associated with reduced short-term mortality (OR 0.48, 95% CI [0.26, 0.89], p = 0.02), lower incidence of postoperative low cardiac output, atrial fibrillation, and MACCEs, as well as shorter intubation duration and hospital stay. Meta-regression did not reveal any associations between pre- or intraoperative variables and short-term mortality. In conclusion, TAG-OPCAB demonstrates favorable short-term outcomes and may be considered a safe and effective strategy in selected patients, while long-term outcomes remain inconclusive due to limited data.

PMID:40268129 | DOI:10.1016/j.amjcard.2025.04.007

Eur J Anaesthesiol. 2025 Jun 1;42(6):500-507. doi: 10.1097/EJA.0000000000002142. Epub 2025 Feb 21.

ABSTRACT

BACKGROUND: The predictability of severe and refractory postpartum haemorrhage (PPH) remains a challenge for clinicians and researchers.

OBJECTIVE: We aimed to evaluate the ability of the shock index to predict refractory PPH.

DESIGN: This study was a secondary analysis of a multicentre, prospective, observational study investigating the association between severe postpartum haemorrhage (PPH) and the subsequent development of mental disorders.

SETTING: Participants were patients who experienced severe PPH, characterised by blood loss of at least 1500 ml requiring the administration of sulprostone. The shock index, defined as the ratio of heart rate to SBP, was recorded at two time points: at the start of sulprostone infusion (T0) and at the time of the most severe symptoms after enrolment but before the occurrence of refractory PPH (T1). Refractory PPH was defined by the need for four or more blood products, interventional radiology, or laparotomy (excluding caesarean section).

THE MAIN OUTCOME: The predictive ability of the shock index was assessed using univariate and multivariate logistic regression and area under the receiver operating characteristic curve (AUROC).

RESULTS: From November 2014 to November 2016, 332 patients experienced severe PPH, of which 316 were included in the final analysis. The prevalence of refractory PPH was 35.4% (112/316). We found that high shock index levels at T0 were independently associated with the occurrence of refractory PPH: odds ratio (OR) 3.07 [95% confidence interval (CI), 1.22 to 7.89, P = 0.017]. In addition, high shock index levels at T1 were also independently associated with the occurrence of refractory PPH: OR 5.28 (95% CI, 2.25 to 12.8), P < 0.001. The AUROC of shock index levels measured at T0 and T1 were 0.614 (95% CI, 0.549 to 0.678) and 0.681 (95% CI, 0.616 to 0.746), respectively.

CONCLUSION: The shock index measured at the start of sulprostone infusion and at the worst time after enrolment, has poor discriminative power to predict this event.

PMID:40265724 | DOI:10.1097/EJA.0000000000002142

Int J Nanomedicine. 2025 Apr 17;20:4919-4942. doi: 10.2147/IJN.S509954. eCollection 2025.

ABSTRACT

INTRODUCTION: Spinal cord injury (SCI) is a severe neurological condition with limited treatment options. Polylactic acid (PLA)+graphene oxide (GO)+anti-TNF-α (Ab) composites have shown potential in regulating immune responses and promoting neural repair.

METHODS: Electrospinning PLA+GO+Ab materials were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and X-ray diffraction (XRD). Their effects on neural stem cells (NSCs) and macrophage polarization were evaluated through in vitro assays, including proliferation, migration, differentiation, and flow cytometry. A rat SCI model was used to assess motor function recovery and histological changes.

RESULTS: PLA+GO+Ab promoted NSC proliferation, migration, and differentiation while inducing macrophage polarization toward the M2 phenotype, reducing inflammation. In the SCI model, PLA+GO+Ab treatment enhanced motor function recovery, reduced spinal cord damage, and promoted axonal regeneration and oligodendrocyte maturation. RNA sequencing identified activation of the Rap1 signaling pathway, contributing to these effects.

DISCUSSION: PLA+GO+Ab composites effectively modulate the neuroimmune microenvironment, supporting SCI recovery by promoting neural repair and immune regulation. These findings suggest its potential as a therapeutic biomaterial for SCI treatment.

PMID:40259915 | PMC:PMC12011040 | DOI:10.2147/IJN.S509954

Saudi J Anaesth. 2025 Apr-Jun;19(2):181-189. doi: 10.4103/sja.sja_829_24. Epub 2025 Mar 25.

ABSTRACT

Chronic postsurgical pain (CPSP) is a prevalent and debilitating sequela of cardiac surgery, exerting a profound impact on patients' quality of life, functional recovery, and healthcare systems. Its pathophysiology includes complex mechanisms, including peripheral and central sensitization, neuroplastic alterations, and inflammatory pathways, influenced by demographic, psychological, and perioperative factors. Inadequate management of acute pain is a critical contributor to its development. This review examines the etiology of CPSP, presents key risk factors, and critically evaluates pharmacological and nonpharmacological interventions. Particular attention is devoted to the role of regional anesthesia techniques and emerging preventive and therapeutic strategies, highlighting the necessity of multidisciplinary, evidence-informed approaches to address this persistent clinical challenge.

PMID:40255354 | PMC:PMC12007855 | DOI:10.4103/sja.sja_829_24

Stem Cell Res Ther. 2025 Apr 18;16(1):189. doi: 10.1186/s13287-025-04319-0.

ABSTRACT

BACKGROUND: Over the past decade, the field of cell therapy has rapidly expanded with the aim to replace and repair damaged cells and/or tissue. Depending on the disease many different cell types can be used as part of such a therapy. Here we focused on the potential treatment of myocardial infarction, where currently available treatment options are not able to regenerate the loss of healthy heart tissue.

METHOD: We generated good manufacturing practice (GMP)-compatible cardiomyocytes (iCMs) from transgene- and xenofree induced pluripotent stem cells (iPSCs) that can be seamless adapted for clinical applications. Further protocols were established for replating and freezing/thawing iCMs under xenofree conditions.

RESULTS: iCMs showed a cardiac phenotype, with the expression of specific cardiac markers and absence of pluripotency markers at RNA and protein level. To ensure a pure iCMs population for in vivo applications, we minimized risks of iPSC contamination using RNA-switch technology to ensure safety.

CONCLUSION: We describe the generation and further processing of xeno- and transgene-free iCMs. The use of GMP-compliant differentiation protocols ab initio facilitates the clinical translation of this project in later stages.

PMID:40251664 | PMC:PMC12008852 | DOI:10.1186/s13287-025-04319-0

Int J Mol Sci. 2025 Mar 27;26(7):3058. doi: 10.3390/ijms26073058.

ABSTRACT

Microgravity, defined by minimal gravitational forces, represents a unique environment that profoundly influences biological systems, including human cells. This review examines the effects of microgravity on biological processes and their implications for human health. Microgravity significantly impacts the immune system by disrupting key mechanisms, such as T cell activation, cytokine production, and macrophage differentiation, leading to increased susceptibility to infections. In cancer biology, it promotes the formation of spheroids in cancer stem cells and thyroid cancer cells, which closely mimic in vivo tumor dynamics, providing novel insights for oncology research. Additionally, microgravity enhances tissue regeneration by modulating critical pathways, including Hippo and PI3K-Akt, thereby improving stem cell differentiation into hematopoietic and cardiomyocyte lineages. At the organ level, microgravity induces notable changes in hepatic metabolism, endothelial function, and bone mechanotransduction, contributing to lipid dysregulation, vascular remodeling, and accelerated bone loss. Notably, cardiomyocytes derived from human pluripotent stem cells and cultured under microgravity exhibit enhanced mitochondrial biogenesis, improved calcium handling, and advanced structural maturation, including increased sarcomere length and nuclear eccentricity. These advancements enable the development of functional cardiomyocytes, presenting promising therapeutic opportunities for treating cardiac diseases, such as myocardial infarctions. These findings underscore the dual implications of microgravity for space medicine and terrestrial health. They highlight its potential to drive advances in regenerative therapies, oncology, and immunological interventions. Continued research into the biological effects of microgravity is essential for protecting astronaut health during prolonged space missions and fostering biomedical innovations with transformative applications on Earth.

PMID:40243850 | PMC:PMC11988870 | DOI:10.3390/ijms26073058

Int J Mol Sci. 2025 Mar 27;26(7):3063. doi: 10.3390/ijms26073063.

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of death globally, with myocardial infarction (MI) being a major contributor. The current therapeutic approaches are limited in effectively regenerating damaged cardiac tissue. Up-to-date strategies for heart regeneration/reconstitution aim at cardiac remodeling through repairing the damaged tissue with an external cell source or by stimulating the existing cells to proliferate and repopulate the compromised area. Cell reprogramming is addressed to this challenge as a promising solution, converting fibroblasts and other cell types into functional cardiomyocytes, either by reverting cells to a pluripotent state or by directly switching cell lineage. Several strategies such as gene editing and the application of miRNA and small molecules have been explored for their potential to enhance cardiac regeneration. Those strategies take advantage of cell plasticity by introducing reprogramming factors that regress cell maturity in vitro, allowing for their later differentiation and thus endorsing cell transplantation, or promote in situ cell proliferation, leveraged by scaffolds embedded with pro-regenerative factors promoting efficient heart restoration. Despite notable advancements, important challenges persist, including low reprogramming efficiency, cell maturation limitations, and safety concerns in clinical applications. Nonetheless, integrating these innovative approaches offers a promising alternative for restoring cardiac function and reducing the dependency on full heart transplants.

PMID:40243729 | PMC:PMC11988544 | DOI:10.3390/ijms26073063

Stem Cells. 2025 May 15;43(5):sxaf018. doi: 10.1093/stmcls/sxaf018.

ABSTRACT

BACKGROUND: When pigs underwent apical resection (AR) on postnatal day (P) 1 (ARP1) followed by myocardial infarction (MI) on P28, the hearts had little evidence of scarring; meanwhile, hearts underwent MI on P28 without ARP1 showed large infarcts on P56; and the improvement of ARP1 hearts was driven primarily by cardiomyocyte proliferation. AR and MI were performed ~5 mm (AR) and ~20 mm (MI) above the heart apex; thus, we hypothesize that ARP1 preserved the cardiomyocytes cell-cycle throughout the left ventricle, rather than only near the resection site.

METHODS: Sections of cardiac tissue were collected from the left ventricle of uninjured pigs and from both the border zone (BZ) of AR and uninjured regions (remote zone, [RZ]) in ARP1 hearts. Cardiomyocyte proliferation was evaluated via immunofluorescence analysis of phosphorylated histone 3 [PH3] and symmetric Aurora B (sAuB). Single nucleus RNA sequencing (snRNAseq) data collected from the hearts of fetal pigs, uninjured pigs, and the BZ and RZ of ARP1 pigs was evaluated via our cell-cycle-specific autoencoder to identify proliferating cardiomyocytes.

RESULTS: Cardiomyocyte PH3 and sAuB expression, and percentage of proliferating cardiomyocytes in snRNA data was significantly more common in both BZ and RZ of ARP1 than uninjured hearts but did not differ significantly between the ARP1-BZ and ARP1-RZ at any time point. Heat shock proteins HSPA5 and HSP90B1 were overexpressed at both ARP1-BZ and ARP1-RZ. In AC16 cell, overexpression (and knockdown) of HSPA5-HSP90B1 increased (and decrease) cell-cycle activity.

CONCLUSION: ARP1 preserved proliferative capacity of cardiomyocytes located throughout the left ventricle.

PMID:40229986 | PMC:PMC12080357 | DOI:10.1093/stmcls/sxaf018