Search Results (1,651)

Interferon Regulatory Factor 5 plays an important role in the regulation of innate immune responses by amplifying the Nuclear Factor κB response, which is critical in gout inflammation. Furthermore, the rs4728141 polymorphism C allele was associated with both increased IRF5 expression and susceptibility to gout. We examine the association between rs4728141 and cytokine production in response to various Toll-Like Receptor ligands and describe the transcriptomic and proteomic changes observed in patients with gout and controls in relation to this polymorphism. We examine the transcriptome of freshly isolated peripheral blood mononuclear cells (PBMCs) from 93 normouricemic donors and 63 gout patients as well as serum inflammatory proteome in 197 control and 195 gout samples. Stimulation experiments of freshly isolated human PBMCs were performed over 24 h, followed by RNA-sequencing in gout patients and cytokine production measurement by ELISA in normouricemic donors and gout patients. The rs4728141 C allele was associated with increased IL-1β expression in unstimulated PBMCs of controls, but not in gout. No association between the polymorphism and serum inflammatory proteome was found. As expected, an increased IRF5 expression was observed in stimulated PBMCs of rs4728141 C allele carriers in response to several stimulations. Interestingly, IL-1β production was specifically enhanced in association to the rs4728141 C allele when cells were stimulated with palmitate with or without monosodium urate crystals. This pattern of cytokine production shows a functional impact of rs4728141 in gout through altered IL-1β production. Full article

Background: Breast reconstruction following mastectomy plays a crucial role in breast cancer management, restoring physical form and significantly impacting psychological well-being and quality of life. Implant-based breast reconstruction (IBBR) is the most performed technique worldwide due to its relative simplicity, shorter operative times, and avoidance of donor site morbidity. Achieving satisfactory aesthetic outcomes, however, remains challenging, as multiple factors—including patient characteristics, surgical technique, implant selection, timing of reconstruction, and adjuvant therapies—can influence the final appearance. Methods: Literature research was performed via PubMed, Scopus and Cochrane Library Database, focusing on studies examining aesthetic outcomes in implant-based breast reconstruction published between 2015 and 2025. Data on type of study, sample size, aesthetic evaluation methods, and duration of follow-up were collected and summarized. Results: Among 747 articles identified, only 25 articles fulfilled inclusion criteria, including mostly retrospective studies, but also prospective studies, randomized clinical trials, and reviews. Factors such as BMI, inframammary fold management, and implant selection were consistently reported to influence aesthetic outcomes. Surgical techniques including ADM use, axillary advancement sutures, hybrid reconstruction with fat grafting, and prepectoral implant placement were associated with improved patient satisfaction. Patient satisfaction often differs from surgeon-assessed outcomes, emphasizing the importance of subjective evaluation. Conclusions: Despite the heterogeneity and retrospective nature of many studies, evidence indicates that optimizing aesthetic outcomes in IBBR relies on careful patient selection, tailored surgical planning, and meticulous use of evidence-based techniques, including implant selection, flap-based support, and adjunctive strategies. Patient-reported outcomes are essential for evaluating success, and future research should focus on standardized outcome measures and prospective studies to further refine reconstructive approaches and maximize both cosmetic satisfaction and quality of life. Full article

Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work using human organoids found that dietary glucose hyperabsorption is a steadfast trait in cultures derived from some obese subjects, but detailed transcriptional or epigenomic features of the intestinal epithelia associated with this persistent phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as non-obese, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subject organoids have significantly upregulated dietary nutrient absorption transcripts and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting predicted that enhanced HNF4G binding may promote the obese hyperabsorption phenotype. Quantitative RT-PCR assessment in organoids representing a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, SLC5A11, and SLC2A5 were highly correlated with hyperabsorption. Thus, the obese hyperabsorption phenotype was characterized by transcriptional changes that support increased nutrient uptake by intestinal epithelia, potentially driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides a new perspective in considering therapeutic targets and options with which to manage the disease. Full article

Aging, one of the main factors associated with cardiovascular diseases, induces vascular modifications through nitric oxide (NO) release and oxidative stress. Based on the antioxidant properties of the non-enzymatic spirulina extract (non-Enz-Spir-E) and that degrading enzymes enhances the extract bioactivity, the aim of this study was to analyze the in vitro effect of an Alcalase-assisted Enz-Spir-E on the vasodilator function of conduit and resistance arteries (which differently contribute to blood pressure regulation) in aging. Therefore, thoracic aorta (TA) and mesenteric arteries (MA) from male Sprague–Dawley rats (20–22 months-old) were divided into two groups: non-incubated vessels and vessels exposed to Enz-Spir-E (0.1% w/v) for 3 h. The vasodilation to acetylcholine (ACh), sodium nitroprusside (SNP, a NO donor), carbon-monoxide-releasing molecule (CORM), and cromakalim (a potassium channel opener), as well as NO and superoxide anion production, were studied. Enz-Spir-E increased the ACh-, SNP-, and CORM-induced responses in both types of arteries, while the cromalakim-induced relaxation was increased only in MA. Enz-Spir-E increased NO release (TA: 5.69-fold; MA: 1.79-fold), while it reduced superoxide anion formation (TA: 0.52-fold; MA: 0.66-fold). These results indicate that Enz-Spir-E improves aging-associated vasodilation through increasing NO release/bioavailability in both types of arteries and hyperpolarizing mechanisms only in MA. Full article

Serological testing for SARS-CoV-2-specific antibodies, particularly those targeting the nucleocapsid protein, plays a key role in assessing past infection and estimating population-level seroprevalence. The seroprevalence of nucleocapsid antibodies against SARS-CoV-2 was evaluated in 1048 blood donors using the Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay. Participants completed a questionnaire to assess risk factors, symptoms during SARS-CoV-2 infection and vaccination status. The overall SARS-CoV-2 seroprevalence was 89.69%. Seroprevalence was not significantly associated with gender or age. In multivariate logistic regression, most investigated risk factors showed no significant association with seroprevalence. However, residence area and vaccination status were independently associated with SARS-CoV-2 seropositivity. Donors from rural areas had significantly higher odds of seropositivity (aOR = 1.68; 95% CI: 1.01–2.79; p = 0.045) compared to those from urban areas. Unvaccinated individuals were more likely to test positive for SARS-CoV-2 compared to vaccinated participants (aOR: 2.59; 95% CI: 1.35–4.99; p = 0.004). After three years of the COVID-19 pandemic, the prevalence of SARS-CoV-2 among blood donors was remarkably high, indicating that the vast majority of this population group had been exposed to the virus. This study highlights the risk factors for SARS-CoV-2 infection and the differences in antibody prevalence between vaccinated and unvaccinated individuals. Our findings underscore the pivotal role of vaccination in controlling the pandemic and provide valuable insights for policymakers in designing targeted strategies to curb future SARS-CoV-2 transmission. Full article

Background: End-stage renal disease (ESRD) affects up to 25% of lung transplant recipients within 10 years. The selection process for kidney transplantation versus dialysis reflects complex clinical decision-making that has not been systematically characterized. Methods: This retrospective observational study analyzed all lung transplant recipients who developed ESRD at our center from 2010 to 2024 (n=32), comparing those receiving kidney transplantation (n = 18) versus those remaining on dialysis (n = 14). We developed an exploratory Clinical Selection Score to retrospectively characterize observed selection patterns and calculated E-values to assess robustness to unmeasured confounding. Results: Kidney transplant recipients were younger (35.7 ± 12.9 vs. 48.4 ± 14.8 years, p = 0.013) with better selection characteristics quantified by our Clinical Selection Score (4.1 ± 0.8 vs. 1.6 ± 1.1 points, p < 0.001). The score showed excellent discrimination (C-statistic 0.82). Living donors were available for 88.9% of transplanted patients versus 0% of dialysis patients. In our selected cohorts, mortality was 22.2% in kidney transplant recipients vs. 78.6% in dialysis patients (p = 0.002), with median survival of 161.6 vs. 126.6 months (p = 0.021). After adjustment for age, kidney transplantation was observed to be associated with 72% lower mortality risk (HR 0.28, 95% CI 0.09–0.89, p = 0.031), though selection bias limits causal interpretation. The E-value of 6.61 suggests robustness to unmeasured confounding. Conclusions: This observational study describes real-world selection patterns and their associated outcomes in lung transplant recipients with ESRD. While carefully selected patients receiving kidney transplantation experienced favorable results, many patients were appropriately managed with dialysis based on medical and non-medical factors. Our analysis provides transparency about selection criteria and outcomes to inform clinical decision-making. Larger multicenter studies are needed to validate these findings and develop prediction tools. Full article

Corneal regeneration has gained growing interest in recent years, largely due to the limitations of conventional treatments and the persistent shortage of donor tissue. Among the emerging strategies, extracellular vehicles (EVs), especially those derived from mesenchymal stromal cells (MSCs), have shown great promise as a cell-free therapeutic approach. These nanoscale vesicles contribute to corneal healing by modulating inflammation, supporting epithelial and stromal regeneration, and promoting nerve repair. Their therapeutic potential is largely attributed to the diverse and bioactive proteomic cargo they carry, including growth factors, cytokines, and proteins involved in extracellular matrix remodeling. This review presents a comprehensive examination of the proteomic landscape of EVs in the context of corneal regenerative medicine. We explore the biological functions of EVs in corneal epithelial repair, stromal remodeling, and neurodegeneration. In addition, we discuss advanced proteomic profiling techniques such as mass spectrometry (MS) and liquid chromatography–mass spectrometry (LC-MS/MS), which have been used to identify and characterize the protein contents of EVs. This review also compares the proteomic profiles of EVs derived from various MSC sources, including adipose tissue, bone marrow, and umbilical cord, and considers how environmental cues, such as hypoxia and inflammation, influence their protein composition. By consolidating current findings, this article aims to provide valuable insights for advancing the next generation of cell-free therapies for corneal repair and regeneration. Full article

Background: Carotid intima-media thickness (CIMT) is an established risk factor for adverse cardiovascular events in the general population, but its impact on patients after heart transplantation (HTX) remains unknown. We investigated the effects of an increased pre-transplant CIMT > 0.9 mm on outcomes after HTX. Methods: This observational retrospective single-center study included 311 patients receiving HTX at Heidelberg Heart Center between 2002 and 2014. Patients were stratified by degree of pre-transplant CIMT (CIMT ≤ or >0.9 mm, threshold defined by ESC guidelines). Analysis covered donor and recipient demographics, post-transplant medications, mortality (including causes of death after HTX), early post-transplant atrial fibrillation (AF), and stroke after HTX. Results: A total of 37 of 311 HTX recipients (11.9%) had a pre-transplant CIMT > 0.9 mm. These patients showed an increased 10-year post-transplant mortality (81.1% versus 41.2%, p < 0.001) and had a higher percentage of death due to graft failure (24.3% versus 10.6%, p = 0.017), as well as due to thromboembolic events/bleeding (10.8% versus 2.9%, p = 0.019). Multivariate analysis demonstrated pre-transplant CIMT > 0.9 mm as an independent risk factor for 10-year mortality after HTX (HR: 2.599, 95% CI: 1.683–4.014, p < 0.001). Secondary outcomes showed a significantly higher rate of 30-day post-transplant AF (27.0% versus 10.9%, p = 0.006) and 30-day stroke after HTX (10.8% versus 1.1%, p < 0.001) in patients with a pre-transplant CIMT > 0.9 mm. Conclusion: Pre-transplant CIMT > 0.9 mm is a prognostic marker for early post-transplant AF, stroke, and reduced long-term survival after HTX. Preventive measures, including close monitoring and management of cardiovascular risk factors, are warranted in these high-risk patients. Full article

The clinical pathway of a patient who experiences cardiac arrest and subsequently dies (with or without organ donation) is complex. It involves uncontrolled (u-) donation after circulatory death (DCD), controlled (c-) DCD, and donor after brain death (DBD). The present paper aims to summarize existing evidence on organ donation rates among out-of-hospital cardiac arrest (OHCA) patients, with a focus on these three donor categories (uDCD, DBD, and cDCD). Furthermore, the potential to expand each donor pathway in OHCA patients will be highlighted, based on available evidence. Among non-survivor OHCA patients, the prevalence of brain death (BD) is estimated to be low, though reported data are not uniform. The diagnosis of BD is made 3 to 6 days after return of spontaneous circulation. The implementation of uDCD is known to be quite challenging due to logistical, ethical, and resource issues. Its rationale is still well grounded, mainly considering two factors: (a) the high incidence of OHCA, such that uDCD donors can be considered an existing pool of potential donors; (b) the uDCD pathway shows feasibility both under organizational (i.e., only lung uDCD program) and clinical views (normothermic regional perfusion, ex vivo machine perfusion, and an appropriate donor–recipient match). Controlled DCDs are donors who died after a planned withdrawal of life-sustaining therapy (WLST). Data on the percentage of cDCD among OHCA patients is not uniform since the percentage of utilized cDCD has been estimated at around 10%. According to available evidence, each donor pathway in OHCA has the potential to be expanded, mainly by the identification of potential donors and the implementation of DCD programs. Full article

Living kidney transplantation offers the best results for end-stage renal disease patients, but concerns about cardiovascular risk after nephrectomy for kidney donors have been raised. We aimed to estimate the contribution of renal function to endothelial dysfunction (ED) and subclinical inflammation in a non-interventional, prospective, multicenter, longitudinal study with two cohorts: living kidney donors and their transplant recipients (registered clinical trial NCT02515643). The measured glomerular filtration rate (mGFR) by iohexol clearance, estimated GFR according to the CKD-EPI and MDRD-4 formulas, and levels of endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin, von Willebrand Factor, pentraxin, and urinary albumin-to-creatinine ratio) and subclinical inflammation biomarkers (sIL-6, sTNF-R1, sTNF-R2, sTWEAK, and high-sensitivity C-reactive protein) were determined at baseline and 1-year follow-up. Fifty pairs of donors and recipients were recruited between 2015 and 2018. Among the endothelial dysfunction biomarkers, sVCAM-1 increased in donors and decreased in recipients (p < 0.01) while, among the inflammation biomarkers, sTNFR1 and sTNFR2 significantly increased in donors and decreased in recipients (p < 0.001). After transplantation, parallel increases and decreases in ED and subclinical inflammation biomarkers were observed in the donor and recipient cohorts, respectively. Long-term follow-up is needed to characterize the cardiovascular risk associated with these changes. Full article

Background/Objectives: A novel treatment of absolute uterine factor infertility is uterus transplantation. In preparation for human surgery, autotransplantation was performed in a sheep model to assess ischemia-reperfusion injury of the uterine wall. Methods: Seven multiparous ewes underwent live-donor uterus autotransplantation; in six, the procedure was completed successfully. Tissue blocks of complete uterine wall, endometrium, and myometrium were obtained at four predefined time points: native (baseline), after 1 h of cold ischemia, after 30 min of warm ischemia, and after 30 min of reperfusion. Samples were analyzed by differential scanning calorimetry and routine hematoxylin–eosin histology. Results: Histology demonstrated preserved epithelial, glandular, and stromal structures, with only minimal, reversible changes that increased with the ischemic duration. Differential scanning calorimetry confirmed alterations in thermal stability: in the uterine wall and myometrium, the calorimetric enthalpy decreased from baseline (3.40 ± 0.53 J/g) to reperfusion (2.62 ± 0.22 J/g), indicating structural loosening; in contrast, the endometrium calorimetric enthalpy slightly increased, suggesting greater flexibility and less susceptibility to ischemia-reperfusion injury. Conclusions: In this preliminary study, differential scanning calorimetry proved to be an effective and sensitive method for detecting early structural alterations in the uterine wall that could negatively impact post-transplant function. Cold and warm ischemia did not cause irreversible damage within a two-hour time frame, supporting the feasibility of short-term preservation in uterus transplantation. The myometrium demonstrated more significant vulnerability than the endometrium, which highlights the necessity of protective strategies to preserve smooth muscle integrity during transplantation. Full article

Background/Objectives: Some lung transplant (LungTx) recipients do not achieve the expected lung function within the first year, a condition known as baseline lung allograft dysfunction (BLAD). Our objective was to analyze the risk factors associated with BLAD, focusing on the variables associated with a higher risk of developing a more intense alloimmune response. Methods: We carried out a prospective study including 88 LungTx recipients. BLAD was defined as failure to reach 80% of the predicted value for forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) on two tests conducted at least three weeks apart. Tacrolimus time in therapeutic range (TTR) and mycophenolic acid area under the curve (MPA AUC_0–12h) were measured at the third month. Donor–recipient compatibility was assessed using HLA eplet mismatch analysis, performed via HLA Matchmaker 3.1. Results: BLAD patients showed greater eplet mismatch burden (67, IQR 20 vs. 55, IQR 22, p = 0.018) and had been exposed to a lower TTR (26.6%, IQR 14.0% vs. 39.6%, IQR 24.3%, p = 0.039) and less frequently to an adequate third-month MPA AUC_0–12 > 30 mg × h/L (57.1% vs. 89.2%, p = 0.020). DR/DQ eplet mismatches (β = −0.348, p = 0.002) and third-month MPA AUC_0–12 (β = 0.285, p = 0.009) were independently associated with six-month predicted FEV1%. Conclusions: Among other variables, BLAD and initial lung graft function are associated with greater eplet discordance and lower immunosuppressive drug exposure, suggesting a potential role of underlying alloimmune responses in their pathogenesis. Full article

This study presents a computational investigation into the design of triphenylamine-based donor chromophores incorporating 2-(1,1-dicyanomethylene)rhodanine as the acceptor unit. Three molecular architectures (System-1 to System-3) were developed by introducing distinct thiophene-derived $\pi$-bridges to modulate their electronic and optical characteristics for potential application in bulk heterojunction organic solar cells (OSCs). Geometrical optimizations were performed at the B3LYP/6-31+G(d,p) level, while excited-state and absorption properties were evaluated using TD-DFT with the CAM-B3LYP functional. Frontier orbital analysis revealed efficient charge transfer from donor to acceptor moieties, with System-3 showing the narrowest HOMO–LUMO gap (1.96 eV) and the lowest excitation energy (2.968 eV). Charge transport properties, estimated from reorganization energies, indicated that System-2 exhibited the most favorable balance for ambipolar transport, featuring the lowest electron reorganization energy (0.317 eV) and competitive hole mobility. Photovoltaic parameters calculated with PC₆₁BM as acceptor predicted superior $V_{oc}$, $J_{sc}$, and fill factor values for System-2, resulting in the highest theoretical power conversion efficiency (10.95%). These findings suggest that $\pi$-bridge engineering in triphenylamine-based systems can significantly enhance optoelectronic performance, offering promising donor materials for next-generation OSC devices. Full article

Acute myeloid leukemia (AML), the second most common type of leukemia in children, is a heterogeneous disease known to be caused by genetic, epigenetic, and transcriptional changes, predominantly somatic and germline abnormalities. Despite significant improvement of overall survival rates, the prognosis of pediatric AML remains unfavorable in comparison with acute lymphoblastic leukemia (ALL), especially in relapsed or refractory settings. The current status and future directions are focused on establishing an accurate diagnosis and treatment strategies based on the genomic background. Next-generation sequencing (NGS) technologies enable a broader understanding of the basis of the disease for the purpose of determining pathology-associated mutations and additional prognostic biomarkers in pediatric AML. This review focuses on providing an overview of the known and possible prognostic factors, as well as genetic landscape of pediatric AML patients and how it can be used to accurately differentiate and risk stratify patients. It also presents potential candidate modifications for risk adjustment and targeted therapy. Furthermore, we describe in this article a case of a 22-month-old male patient with relapsed M5 high-risk group (HRG) AML with complex karyotype. Due to belonging to the HRG, as well as unsatisfactory chemotherapy response, the patient underwent matched unrelated donor (MUD) stem cell transplantation (SCT). Full article

Background and Objectives: Early allograft dysfunction (EAD), defined as suboptimal initial graft function following liver transplantation (LT), is a serious complication associated with increased post-LT morbidity and mortality. This study aimed to evaluate the impact of EAD on clinical outcomes and to identify associated risk factors. Materials and Methods: Ninety-three patients who underwent LT between July 2015 and August 2024 were retrospectively analyzed. EAD was defined by the presence of one or more of the following criteria: total bilirubin ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on postoperative day 7, and alanine or aspartate aminotransferase levels > 2000 IU/L within the first 7 days. Results: EAD occurred in 20 patients (21.5%). Patients with EAD exhibited significantly lower graft survival (p < 0.01) and patient survival (p = 0.03) compared with those without EAD. EAD was an in-dependent risk factor for both graft survival (p = 0.021) and patient survival (p = 0.027). Acute liver failure (odds ratio [OR], 6.228; 95% confidence interval [CI], 1.179–32.906; p = 0.031), donor age (OR, 1.051; 95% CI, 1.008–1.096; p = 0.020), and warm ischemic time (OR, 1.048; 95% CI, 1.001–1.098; p = 0.046) were identified as significant predictors of EAD development. Conclusions: EAD adversely affects both graft and patient survival following LT. Recipient clinical status, donor age, and intraoperative conditions should be carefully considered to minimize the risk of EAD. Full article