Bosnian Journal of Basic Medical Sciences (BJBMS)
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Comparing del Nido and St. Thomas II cardioplegia in a rat ischemia–reperfusion model: Histopathology, mitochondria, and TEM analysis
Get PDFMyocardial ischemia–reperfusion (IR) injury remains a major challenge in cardiac surgery, and comparative histological and ultrastructural data on cardioplegia solutions are limited. This study compared the myocardial protective effects of St. Thomas II and del Nido cardioplegia in a controlled rat IR model, focusing on inflammation, mast cell dynamics, and subcellular preservation. Twenty-four Wistar Albino rats were randomized to Control, St. Thomas II, or del Nido groups. After 90 minutes of ischemia and 30 minutes of passive reperfusion, myocardial tissue was analyzed by hematoxylin–eosin, toluidine blue, and transmission electron microscopy. Outcomes included mast cell counts, leukocyte infiltration, karyolysis, and ultrastructural measures (Flameng score, crista density, basement membrane thickness). Both cardioplegia groups preserved myocardial morphology and attenuated inflammatory changes versus control. Light microscopy revealed a consistent mast cell density and reduced karyolysis in hearts treated with cardioplegia, with no significant differences observed between St. Thomas II and del Nido solutions. Conversely, transmission electron microscopy (TEM), the primary endpoint of this study, demonstrated enhanced mitochondrial and endothelial preservation in the del Nido group, as evidenced by significantly lower Flameng scores and increased crista density compared to both St. Thomas II and control groups (p < 0.05). In conclusion, both solutions reduced early IR-related injury, but del Nido provided a significant ultrastructural advantage on TEM despite similar routine light-microscopic findings
Efficacy and safety of CalliSpheres drug-eluting bead bronchial arterial infusion chemoembolization vs. bland embolization in advanced lung cancer with hemoptysis: A multicenter retrospective study
Get PDFMassive hemoptysis is a life-threatening complication in patients with advanced primary lung cancer, and effective, safe treatments are crucial. This study aimed to investigate the efficacy and safety of CalliSpheres drug-eluting bead bronchial arterial infusion chemoembolization (DEB-BACE) for managing this condition. A retrospective analysis included 144 patients with advanced primary lung cancer and massive hemoptysis treated at multiple hospitals from January 2019 to January 2023. Patients undergoing bronchial artery embolization were divided into two groups: the observation group (n=76) received CalliSpheres DEB-BACE with epirubicin, and the control group (n=68) received 8spheres blank embolization. Both groups achieved successful hemostasis, with no statistically significant difference in success rates (observation group: 88.16%, control group: 86.76%). However, the observation group had a significantly longer median duration without hemoptysis (96 days vs. 50 days). Two months post-therapy, the observation group showed higher objective response rates (82.89% vs. 38.24%) and disease control rates (92.11% vs. 66.18%) compared to the control group. Adverse reactions were manageable and similar between groups, with no serious complications observed. By January 31, 2024, the observation group had significantly longer median overall survival (11 months vs. 7 months). The DEB-BACE treatment demonstrates safety and efficacy in managing massive hemoptysis in patients with advanced lung cancer. However, the superiority of this approach over bland embolization remains to be established through well-designed prospective studies. Future research is anticipated to provide a definitive comparison and further validate the role of DEB-BACE in clinical practic
L-theanine promotes angiogenesis in limb ischemic mice by modulating NRP1/VEGFR2 signaling
Get PDFPeripheral artery disease (PAD), primarily caused by atherosclerosis, leads to the narrowing or blockage of arteries that supply blood to the limbs. This study explores the pro-angiogenic effects of L-theanine and its underlying mechanisms in a mouse model of hindlimb ischemia (HLI). To evaluate L-theanine’s pro-angiogenic effects, human umbilical vein endothelial cells (HUVECs) were subjected to tube formation, migration, sprouting, and proliferation assays. In vivo, C57BL/6 mice with induced HLI were treated with L-theanine. Blood flow recovery was measured via Doppler ultrasound, and vascular density was analyzed using immunofluorescence staining. RNA sequencing identified neuropilin-1 (NRP1) as a key regulator, and the expression levels of NRP1 and VEGFR2 were examined through qPCR and Western blotting. L-theanine significantly enhanced angiogenesis in HUVECs, as demonstrated by improved tube formation, migration, sprouting, and proliferation. In mice, L-theanine treatment resulted in increased vessel density and improved blood flow recovery. Furthermore, L-theanine was found to activate the NRP1/VEGFR2 signaling pathway in both HUVECs and the HLI mouse model. These findings indicate that L-theanine can promote angiogenesis and activate key pathways involved in vascular repair, suggesting its potential as a therapeutic agent for treating vascular defects associated with PAD
Pathological roles of ubiquitination and deubiquitination systems in sepsis-induced myocardial dysfunction
Get PDFSepsis-induced myocardial dysfunction (SIMD) is a severe complication of sepsis, characterized by impaired cardiac function and high mortality rates. Despite significant advances in understanding sepsis pathophysiology, the molecular mechanisms underlying SIMD remain incompletely elucidated. Ubiquitination and deubiquitination, critical post-translational modifications (PTMs) regulating protein stability, localization, and activity, play pivotal roles in cellular processes, such as inflammation, apoptosis, mitochondrial function, and calcium handling. Dysregulation of these systems has been increasingly implicated in the pathogenesis of SIMD. This review provides a comprehensive overview of the pathological mechanisms driving SIMD, with a focus on the classification and functions of E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), their regulatory systems, and their involvement in SIMD. Dysfunction of the ubiquitin-proteasome system (UPS), often driven by altered activity of E3 ligases, accelerates the degradation of critical regulatory proteins, thereby exacerbating cardiac inflammation, oxidative stress, and apoptosis. Concurrently, imbalances in DUB activity disrupt protein homeostasis, further amplifying myocardial injury. Emerging research underscores the therapeutic potential of targeting these systems. Strategies aimed at modulating E3 ligase activity or restoring DUB balance have shown promise in preclinical studies. This review summarizes current findings on the roles of ubiquitination and deubiquitination in SIMD pathogenesis, highlights the key challenges in advancing this field, and proposes directions for future research
A preliminary study on the prognostic significance of cysteine-rich EGF ligand domain 2 protein (CRELD2) in patients with triple negative breast cancer
Get PDFThe cysteine-rich epidermal growth factor ligand domain 2 protein (CRELD2) is associated with pathways that regulate epithelial-to-mesenchymal transition, a critical process driving cancer metastasis. This study aimed to determine the prognostic value of CRELD2 status on survival outcomes in triple-negative breast cancer (TNBC). Seventy patients were included in the study. Thirty-four patients were metastatic, and 36 patients were non-metastatic. CRELD2 protein expression in tumor tissue was determined by immunohistochemical staining (IHC). The patients were divided into two groups: CRELD2 positive and negative groups. Clinicopathological features and survival outcomes were compared between the groups. In the survival analysis of the non-metastatic patient group, five-year overall survival (OS) rate was 91.7% in the CRELD2-positive patient group and 91% in the negative group (P = 0.91). Median progression free survival (PFS) was 9.4 (95% confidence interval [CI]: 6.4–12.4) months in the CRELD2-positive group and 11.9 (95% CI: 8.2–18.6) months in the CRELD2-negative group (P = 0.04). The median OS was 17.2 (95% CI: 13.7–22.3) months in the CRELD2-positive group and 24.7 (95% CI: 21.8–29.6) months in the CRELD2-negative group (P = 0.02). In multivariate analysis, CRELD2 status (negative vs positive) (hazard ratio [HR]: 0.50, 95% CI: 0.38–0.96, P = 0.02) was determined to be a risk factor for OS and CRELD2 status (negative vs positive) (HR: 0.82, 95% CI: 0.33–0.96, P = 0.01) was defined as a risk factor for PFS in patients with metastatic TNBC. This is the first clinical study to determine the effect of CRELD2 on survival and as a prognostic marker in patients with triple metastatic breast cancer. These results need to be validated prospectively with a large sample size
Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis
Get PDFColorectal cancer (CRC) represents a significant global health challenge. Although telomere maintenance plays a crucial role in tumorigenesis, the prognostic value and immunotherapeutic relevance of telomere maintenance genes (TMGs) in CRC remain poorly understood. In this study, relevant data were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. TMG scores were calculated using the single-sample gene set enrichment analysis (ssGSEA) method, and TMGs associated with prognosis were subsequently identified. TCGA-CRC samples were classified into subtypes via consensus clustering (ConsensusClusterPlus). A risk prediction model was then constructed using univariate and Lasso Cox regression analyses. Survival analysis was performed using Kaplan–Meier curves generated with the survival package. Key genes were validated in vitro using cellular models. Immune cell infiltration was evaluated through ssGSEA, TIMER, and MCP-Counter tools, and chemotherapy responses were predicted using the pRRophetic package. From 28 prognosis-related TMGs, two distinct CRC subtypes were established, with subtype C1 demonstrating more favorable clinical outcomes. Additionally, a risk model incorporating seven TMG-related genes (CDC25C, CXCL1, RTL8C, FABP4, ITLN1, MUC12, and ERI1) was developed for CRC prognosis. Differential mRNA expression levels of these genes were confirmed between CRC cell lines and normal control cells. Furthermore, silencing MUC12 suppressed CRC cell migration and invasion in vitro. Importantly, CRC patients classified as low-risk exhibited superior responses to immunotherapy, whereas high-risk patients showed increased sensitivity to conventional anti-cancer treatments. This study represents the first systematic evaluation of TMGs in CRC prognosis and immunotherapy, providing novel insights that could inform personalized therapeutic strategies
The regulatory role of exercise in heart failure and myocardial energy metabolism: A review
Get PDFMyocardial energy metabolism is crucial for maintaining optimal heart function. The heart, having limited energy storage capacity, is dependent on a continuous energy supply; any disruptions or alterations in energy metabolism pathways can lead to insufficient myocardial energy, potentially triggering heart failure (HF). Exercise, as a safe and economical non-pharmacological intervention, is widely recognized to enhance cardiovascular health and modify myocardial energy metabolism patterns. However, the specific mechanisms by which exercise regulates myocardial metabolism to prevent and treat HF remain unclear. This review aims to detail the characteristics of myocardial metabolism under normal physiological and HF conditions, to further explore the impact of different exercise modalities on myocardial metabolism, and to summarize the molecular mechanisms by which exercise protects the heart by optimizing myocardial energy metabolism. Ultimately, this article aims to provide an in-depth understanding and evidence for the application of exercise interventions in cardiac rehabilitation
Skin pathology in ALS: Diagnostic implications and biomarker potential
Get PDFAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain, resulting in motor deficits and muscle atrophy. Approximately 5–10% of ALS patients are familial (fALS), while the rest are sporadic (sALS). Currently, early diagnosis of ALS cannot be achieved based on clinical manifestations and electromyography due to the lack of effective and easily available biomarkers. The skin and central nervous system (CNS) share the same embryonic origin. Several skin biomarkers have been found in many neurodegenerative diseases, such as abnormal deposition of pathological α-synuclein (α-Syn) in Parkinson\u27s disease. Thus, molecular changes in the skin associated with ALS-specific pathological events could readily be detected and become biomarkers for ALS through skin testing. Here, we summarize the literature on pathological changes in the skin of ALS patients and animal models, including structural abnormalities of the skin, reduced density of skin nerve fibers, abnormal protein aggregation, altered mitochondrial morphology and function, and dysregulation of skin inflammation, which may be useful for early diagnosis and monitoring of ALS progression
Effect of SGLT2 inhibitors on liver fat content: A meta-analysis
Get PDFMetabolic dysfunction-associated steatotic liver disease (MASLD) is a major metabolic disorder linked to increased morbidity and mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, commonly used to manage type 2 diabetes (T2DM), have shown potential in reducing liver fat content (LFC). However, the magnitude and consistency of this effect remain uncertain. This meta-analysis aimed to evaluate the impact of SGLT2 inhibitors on LFC in adults with metabolic disorders. A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted up to January 2, 2024, to identify randomized controlled trials (RCTs) assessing the effects of SGLT2 inhibitors on LFC. Studies were included if they reported liver fat changes measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) or proton magnetic resonance spectroscopy (¹H-MRS). We pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) using a random-effects model to account for variability across studies. Thirteen RCTs with 14 datasets (n = 791 participants) were included. SGLT2 inhibitors significantly reduced LFC compared to controls (SMD: −0.73, 95% CI: −0.97 to −0.50; P < 0.001), with moderate heterogeneity (I² = 62%). Subgroup and meta-regression analyses did not identify any study characteristics—such as study design, diabetic status, patient demographics, baseline LFC, type of SGLT2 inhibitor, or treatment duration—as significant contributors to heterogeneity (all P > 0.05). In conclusion, SGLT2 inhibitors are associated with a significant reduction in LFC in adults, supporting their potential role in managing MASLD
Deep learning and inflammatory markers predict early response to immunotherapy in unresectable NSCLC: A multicenter study
Get PDFImmune checkpoint inhibitors (ICIs) demonstrate substantial interpatient variability in clinical efficacy for unresectable non-small cell lung cancer (NSCLC), underscoring the unmet need for noninvasive biomarkers to predict early therapeutic responses and improve survival outcomes. To address this, we developed a CT-based deep learning model integrated with the systemic immune-inflammatory-nutritional index (SIINI) for early prediction of ICI response. In a retrospective multicenter study of 265 patients treated with ICIs (incorporating chest CT and laboratory data), the cohort was divided into training (70%), internal validation (30%), and external validation sets. The combined model—leveraging DenseNet121-derived deep radiomic features alongside SIINI—achieved strong predictive performance, with AUCs of 0.865 (95% CI: 0.7709–0.9595) in the internal validation cohort and 0.823 (95% CI: 0.6627–0.9827) in the external validation cohort. Gradient-weighted class activation mapping (Grad-CAM) highlighted key CT regions contributing to model predictions, enhancing interpretability for clinical application. These findings highlight the potential of integrating deep learning with inflammatory biomarkers to support personalized ICI therapy in unresectable NSCLC. Future directions include incorporating multi-omics biomarkers, expanding multicenter validation, and increasing sample sizes to further improve predictive accuracy and facilitate clinical translation