Search Results (42)

Pain arising from the lumbosacral region is a recognized cause of poor performance and impaired welfare in horses. However, structural changes in the intertransverse joints (ITJs), lumbar articular process joints (APJs), and lumbosacral intervertebral discs (LSDs) may also occur in asymptomatic horses, complicating interpretation of imaging findings.This study evaluated these structures in 14 middle-aged Warmblood cadavers that were not lame according to the owners prior the onset of the problem that resulted in euthanasia or slaughter and correlated ultrasonographic (US) and computed tomographic (CT) findings with histopathology. Transrectal US was used to assess ITJs and LSDs, followed by helical CT. Histological examination was performed on randomly selected specimens (ITJs n = 13, APJs n = 5, LSDs n = 5). Imaging and histological scores were analyzed using Spearman’s rank correlation. Mild imaging abnormalities were common across all structures. In intertransverse joints, CT findings correlated significantly with histological scores (ρ = 0.679, p = 0.011), whereas US findings did not. APJs had mild CT changes without significant association with histology. LSDs had subtle imaging changes, with a significant correlation between US and CT scores (ρ = 0.748, p < 0.01) but not with histopathology. Overall, mild imaging changes were frequent and may reflect adaptive or early maladaptive modeling rather than clinically relevant disease. Full article

Background/Objectives: The apelin/APJ system has demonstrated neuroprotective effects in experimental studies by regulating key pathogenic mechanisms of ischemic stroke, including oxidative stress, apoptosis, cerebral edema, and inflammation. This study aimed to investigate the role of serum apelin levels measured within the first 24 h in predicting 28-day and long-term mortality in patients with ischemic cerebrovascular disease. Methods: This prospective cohort study included 44 patients hospitalized with a diagnosis of acute ischemic stroke due to large artery atherosclerosis. Serum apelin levels were measured using the ELISA method from blood samples obtained within the first 24 h after symptom onset. Patients were prospectively followed for 28-day and long-term mortality. Results: During the follow-up period, 32.6% of the patients died. The median serum apelin level was significantly higher in the deceased group compared to the survivors [105.0 pg/mL vs. 55.8 pg/mL]. In ROC analysis, the area under the curve (AUC) for apelin in predicting mortality was 0.727 (95% CI: 0.550–0.903). The optimal cut-off value was determined as ≥70.47 pg/mL (sensitivity: 85.71%, specificity: 62.07%). In Kaplan–Meier analysis, the 28-day mortality rate was 52.2% in the high-apelin group (≥70.47 pg/mL), whereas it was 10.0% in the low-apelin group (<70.47 pg/mL) (p = 0.004). In multivariate Cox regression analysis, an apelin level <70.47 pg/mL was identified as an independent prognostic factor (HR: 0.16; 95% CI: 0.03–0.94). The cumulative survival rates at days 28, 56, and 180 were 56.1%, 46.7%, and 11.7%, respectively, in the high-apelin group, while these rates were 100%, 100%, and 81.8%, respectively, in the low-apelin group. The mean NIHSS score was significantly higher in the high-apelin group, and a strong, positive, and highly significant correlation was found between serum apelin level and NIHSS score (r = 0.703, p < 0.001). Conclusions: High serum apelin levels measured within the first 24 h in acute ischemic stroke are associated with increased 28-day and long-term mortality. The association of high endogenous apelin levels with poor prognosis in the clinical setting suggests that apelin is mobilized as a stress response during ischemia, and that elevated circulating levels may actually reflect the severity of the ischemic insult. Full article

The mechanisms underlying doxorubicin (DOX) cardiotoxicity include activation of the renin–angiotensin–aldosterone system (RAAS), oxidative stress, mitochondrial dysfunction, calcium overload, and cardiomyocyte apoptosis. Cortisol plays a key role in regulating multiple metabolic, immunological, cardiovascular, and neuroendocrine processes and may additionally influence drug pharmacokinetics by modulating the activity of P-glycoprotein (P-gp). The peptide apelin, through its specific target, angiotensin II protein J receptor (APJ), exerts cardioprotective, antifibrotic, and anti-inflammatory effects. The available data demonstrate that apelin signaling protects against DOX-induced cardiotoxicity, impacts cortisol secretion, and inhibits RAAS. Short-term elevation in cortisol levels, caused by apelin, may reduce inflammation and thus have cardioprotective properties. However, through chronically elevated cortisol levels, apelin may indirectly contribute to peripheral resistance, cardiac remodeling, and myocardial damage, especially when cortisol metabolism by 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) is altered. This narrative review explores the potential molecular and cellular mechanisms shaping the outcome of apelin–cortisol interplay, offering a potential foundation for developing cardioprotective strategies during anticancer therapy. Future studies should be aimed at assessing the complex interactions between cortisol, apelin, and the RAAS regarding DOX-induced cardiotoxicity. Full article

Elabela (ELA/APELA/Toddler) is an endogenous peptide ligand of the apelin receptor APLNR (also known as APJ) and, together with apelin, forms the apelinergic signalling system. Its role in embryonic development, the cardiovascular system, the kidneys and the endothelium is becoming increasingly well characterised, whilst its function in metabolic regulation remains unresolved. Elabela activates pathways essential for metabolic homeostasis—PI3K/Akt, AMPK-related pathways, redox regulation, inflammatory control and pro-survival cascades—but no study has shown that it directly regulates adipocyte lipid metabolism. This narrative review categorises the evidence at the receptor, organ, immunometabolic and intra-adipocyte levels, and also considers the adipose tissue microenvironment as a distinct level of potential relevance. The available data support a role for Elabela as a candidate mediator of lipid-related metabolic dysfunction—via anti-inflammatory, antioxidant and tissue-protective mechanisms—with macrophage lipid metabolism representing the most informative immunometabolic interface. Human studies remain scarce, heterogeneous and limited by a lack of standardisation in assay methods and the unresolved specificity of isoforms. Elabela should therefore be regarded as a candidate indirect modulator of metabolic homeostasis and a candidate biomarker of cardiometabolic stress or adaptation—not as a confirmed direct regulator of adipocyte lipid metabolism. Full article

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction, vascular remodeling, and a sustained increase in pulmonary vascular resistance, causing cardiopulmonary damage. The apelin receptor (APJ), a member of the G protein-coupled receptor family, has emerged as an essential modulator of vascular homeostasis. Clinical and preclinical studies have demonstrated that its activation exerts beneficial effects on the progression of PAH. Its main actions include the restoration of endothelial function, reactivation of the BMPR2/SMAD axis, induction of nitric oxide-mediated vasodilation, inhibition of autophagy and the migration of the pulmonary artery smooth muscle cells (PASMCs). Furthermore, its expression and functionality are modulated by epitranscriptomic mechanisms, particularly by microRNAs involved in the post-transcriptional regulation of key genes for vascular homeostasis. These findings position the APJ as a relevant therapeutic target in PAH. However, the clinical application of its agonists still faces pharmacokinetic limitations that restrict their therapeutic use. Therefore, the aim of this review is to gather current information on APJ in the pathophysiology of PAH and focus attention on its potential as a therapeutic target. Full article

Ischemia–reperfusion injury (IRI) refers to a paradoxical pathological process in which ischemic tissues or organs sustain further damage upon the restoration of blood flow and is clinically commonly observed in the peripheral vascular systems and various vital organs. In 2013, the endogenous peptidic hormone ELABELA (ELA) was identified as a novel native ligand of the APJ G protein-coupled receptor, alongside apelin. ELA is constitutively expressed in a range of adult and embryonic tissues and plays a role in numerous physiological and pathological processes. In recent years, a rapidly growing body of research has highlighted the cytoprotective properties of ELA against IRI. In this review, we synthesize current research on the protective role of ELA in mitigating IRI across multiple organ systems. Full article

Anatomical variations of the caudal ventral lamina of the sixth cervical vertebra (C6), referred to as equine caudal cervical morphologic variations (ECCMV), and radiographic modelling of the caudal cervical articular process joints (APJ) are commonly identified in sport horses, yet their interrelationship and relevance for athletic performance remain controversial. This retrospective observational study aimed to determine the prevalence of ECCMV and APJ modelling in a clinically sound warmblood sport horse population, to evaluate a potential association and to assess if ECCMV affects competition performances. Records of 200 warmbloods, presented for pre-purchase examination between 2020 and 2024 were reviewed: the predominant breed was Hanoverian (n = 131), followed by Oldenburg (n = 27) and Holsteiner (n = 22), including 127 geldings, 61 mares and 12 stallions with a median age of 5. ECCMV was diagnosed on latero-lateral radiographs if the caudal ventral lamina of C6 was uni- or bilaterally absent, and APJ modelling at C6/C7 was graded as either normal or mild or moderate to severe. Competition placings and lifetime earnings of each horse were collected from the German National Equestrian Federation database. ECCMV was found in 30% of horses and APJ modelling in 32.5% (mild 26.5%, moderate/severe 6%). There was no significant association between the presence of ECCMV, APJ alterations and competition results, but horses with ECCMV were less likely to exhibit radiographic changes in the adjacent APJ compared to those with a normal C6 morphology (23.3% vs. 36.4%). In conclusion, ECCMV is a common anatomical variation in clinically sound warmbloods, neither predisposing them to APJ modelling nor limiting athletic performance. Full article

The proliferation of Internet of Things (IoT) devices has created unprecedented security challenges characterized by resource constraints, heterogeneous network architectures, and severe class imbalance in attack detection datasets. This paper presents a comprehensive benchmark evaluation of five Generative Adversarial Network (GAN) architectures for energy-aware intrusion detection: Standard GAN, Progressive GAN (PGAN), Conditional GAN (cGAN), Graph-based GAN (GraphGAN), and Wasserstein GAN with Gradient Penalty (WGAN-GP). Our evaluation framework introduces novel energy-normalized performance metrics, including Accuracy-per-Joule (APJ) and F1-per-Joule (F1PJ), that enable principled architecture selection for energy-constrained deployments. We propose an optimized WGAN-GP architecture incorporating diversity loss, feature matching, and noise injection mechanisms specifically designed for classification-oriented data augmentation. Experimental results on a stratified subset of the BoT-IoT dataset (approximately 1.83 million records) demonstrate that our optimized WGAN-GP achieves state-of-the-art performance, with 99.99% classification accuracy, a 0.99 macro-F1 score, and superior generation quality (MSE 0.01). While traditional classifiers augmented with SMOTE (i.e., Logistic Regression and CNN1D-TCN) also achieve 99.99% accuracy, they suffer from poor minority class detection (77.78–80.00%); our WGAN-GP improves minority class detection to 100.00% on the reported test split (45 of 45 attack instances correctly identified). Furthermore, WGAN-GP provides substantial efficiency advantages under our energy-normalized metrics, achieving superior accuracy-per-joule performance compared to Standard GAN. Also, a cross-dataset validation across five benchmarks (BoT-IoT, CICIoT2023, ToN-IoT, UNSW-NB15, CIC-IDS2017) was implemented using 250 pooled test attacks to confirm generalizability, with WGAN-GP achieving 98.40% minority class accuracy (246/250 attacks detected) compared to 76.80% for Classical + SMOTE methods, a statistically significant 21.60 percentage point improvement ($p<0.0001$). Finally, our analysis reveals that incorporating diversity-promoting mechanisms in GAN training simultaneously achieves best generation quality AND best classification performance, demonstrating that these objectives are complementary rather than competing. Full article

The apelin–ELABELA–APJ axis, collectively known as the apelinergic system, has emerged as a key regulator of cardiovascular homeostasis. Acting through G-protein-coupled mechanisms, it modulates vascular tone, cardiac contractility, angiogenesis, fluid balance, and metabolism. Growing evidence indicates that dysregulation of apelinergic signaling contributes to the development and progression of atherosclerosis, hypertension, and heart failure. Experimental studies demonstrate cardioprotective actions of apelin and ELABELA, including anti-fibrotic, anti-inflammatory, vasodilatory, and pro-angiogenic effects, whereas some findings suggest context-dependent pro-atherogenic or vasoconstrictive roles. Clinical data show that circulating apelinergic peptides vary across cardiovascular conditions, being upregulated in acute coronary syndromes and diminished in chronic ischemic or hypertensive disease. In heart failure, early compensatory activation is followed by progressive depletion, and low ELABELA levels correlate with disease severity. Moreover, the apelinergic system may exert anti-arrhythmic effects through modulation of myocardial electrophysiology and structural remodeling. Novel synthetic APJ agonists and stabilized peptide analogs show promising preclinical efficacy in reducing cardiac remodeling, improving contractility, and lowering blood pressure. Altogether, the apelinergic pathway represents a multifaceted modulator and a promising therapeutic target in cardiovascular medicine, warranting further translational studies to elucidate its diagnostic and treatment potential. Full article

Background and Objectives: Apelin-13 and its receptor (APJ) are increasingly recognized as key regulators of metabolic pathways that may contribute to the pathophysiology of obstructive sleep apnea (OSA) syndrome. This study aimed to investigate the relationship between circulating apelin-13 and APJ levels with disease severity in patients diagnosed with OSA, considering the impact of obesity. Materials and Methods: A total of 105 subjects were enrolled: 35 obese patients with OSA, 35 non-obese patients with OSA, and 35 healthy controls. Demographic data, polysomnographic parameters, metabolic markers, Apelin-13, and APJ levels were compared across groups. Patients were further classified as mild-moderate, or severe OSA for subgroup analysis. Correlations between Apelin-13, APJ, BMI, minimum oxygen saturation (Min SaO₂), and apnea–hypopnea index (AHI) were assessed. ROC analysis was used to examine the potential of Apelin-13 and APJ to predict severe OSA. Results: Apelin-13 levels were significantly higher in obese patients with OSA compared to non-obese OSA and controls (p < 0.001), whereas APJ levels were lowest in obese OSA subjects. Apelin-13 showed significant positive correlations with BMI (r = 0.63, p < 0.001) and AHI (r = 0.33, p = 0.005), and a negative correlation with Min SaO₂ (r = −0.35, p = 0.004). Conversely, APJ levels were negatively correlated with BMI (r = −0.60, p < 0.001) and AHI (r = −0.40, p = 0.002) and positively correlated with minimum SaO₂ (r = 0.40, p = 0.002). In severe OSA, insulin and HOMA-IR levels were significantly higher than in mild-moderate OSA (p = 0.02 and p = 0.003, respectively). However, there was no significant difference in Apelin-13 and APJ levels by OSA severity category. ROC analysis revealed that neither Apelin-13 nor APJ demonstrated sufficient diagnostic performance to predict severe OSA (AUC = 0.50 and 0.63, respectively). Conclusions: Apelin and APJ levels are correlated with key metabolic and hypoxic parameters in OSA, indicating that the apelin/APJ system may play a compensatory role in mitigating hypoxia-induced and metabolic complications. However, neither marker alone provides sufficient predictive value for disease severity, emphasizing the need for further studies to clarify the mechanisms and potential clinical applications of this system in OSA management. Full article

de Grijs and Bono (ApJS 2020, 246, 3) compiled a list of distances to M87 from the literature published in the last 100 years. They reported the arithmetic mean of the three most stable tracers (Cepheids, tip of the red giant branch, and surface brightness fluctuations). The arithmetic mean is one of the measures of central tendency of a distribution; others are the median and mode. The three do not align for asymmetric distributions, which is the case for the distance moduli ${\mu }_0$ to M87. I construct a kernel density distribution of the set of ${\mu }_0$ and estimate the recommended distance to M87 as its mode, obtaining ${\mu }_0=\left(31.06\pm 0.001{\left(\mathrm{statistical}\right)}_{-0.06}^{+0.04}\left(\mathrm{systematic}\right)\right)$ mag, corresponding to $D={16.29}_{-0.45}^{+0.30}$ Mpc, which yields uncertainties smaller than those associated with the mean and median. Full article

Background: Peptides of the apelinergic system may participate in the development of atherosclerosis, but their role in atherogenesis is unclear. The aim of the study was to evaluate the levels of apelinergic system peptides, such as Elabela (Ela), apelin-13 (AP-13), apelin-17 (AP-17) and apelin receptor (APJ) in the serum and epicardial adipose tissue (EAT) of patients with multivessel coronary artery disease (CAD) who underwent myocardial revascularisation surgery. Methods: The participants comprised 51 CAD patients and 34 healthy adults. Concentrations of Ela, AP-13, AP-17 and APJ were determined by ELISA kits. We analysed the demographics, and clinical and laboratory parameters of the CAD patients. Results: We showed that the serum Ela and AP-17 levels significantly decreased, and APJ significantly increased, in the CAD patients in comparison to the healthy control. A significant relationship between the serum and EAT concentrations of Ela and APJ (p < 0.05) was observed. Positive correlations were found between the serum levels of AP-13 and AP-17, and between AP-17 and APJ. There was a positive correlation between the tissue levels of AP-17 and APJ. The tissue Ela concentration negatively correlated with the BMI, TCH and LDL levels. AP-13 in EAT was negatively associated with the glucose level. In contrast, the tissue APJ showed a positive correlation with TCH concentration. Good diagnostic potential of ELA, AP-17 and APJ was observed for CAD prediction (p < 0.001 for all). Conclusions: The results indicate that the levels of apelinergic peptides are altered in patients with CAD, which may be a potential diagnostic indicator. Full article

The apelinergic system exerts multiple biological activities in human pathologies, including cancer. Overactivation of apelin/APJ, which has been detected in many malignant tumors, and the strong correlation with progression-free and overall survival, suggested the role of an oncogene for the apelin gene. Emerging evidence sheds new light on the effects of apelin on cellular functions and homeostasis in cancer cells and supports a direct role for this pathway on different hallmarks of cancer: “sustaining proliferative signaling”, “resisting cell death”, “activating invasion and metastasis”, “inducing/accessing vasculature”, “reprogramming cellular metabolism”, “avoiding immune destruction” and “tumor-promoting inflammation”, and “enabling replicative immortality”. This article reviews the currently available literature on the intracellular processes regulated by apelin/APJ, focusing on those pathways correlated with tumor development and progression. Furthermore, the association between the activity of the apelinergic axis and the resistance of cancer cells to oncologic treatments (chemotherapy, immunotherapy, radiation) suggests apelin/APJ as a possible target to potentiate traditional therapies, as well as to develop diagnostic and prognostic applications. This issue will be also covered in the review. Full article

Apelin serves as the endogenous ligand for the APJ receptor and enhances cardiac contractility without significantly affecting potassium currents. However, its short in vivo half-life limits clinical application, prompting the development of metabolically stable APJ receptor agonists. This study employed the patch-clamp technique to investigate the effects of the C-terminally modified apelin-13-2Nal derivative (2Nal) on action potential dynamics, rapid sodium (I_Na), and transient potassium (I_TO) currents in rat cardiomyocytes. We discovered that 2Nal prolongs ventricular action potential duration by selectively blocking I_To. Dose-response analysis indicated that 2Nal acts as a partial antagonist of I_TO, achieving a maximum blockade of 47%, with an apparent EC50 of 0.3 nM, while not affecting I_Na. Our lab previously found that an imbalance between I_To and I_Na currents contributes to the development of cardiac arrhythmias in conditions like Brugada syndrome. Currently, few therapeutic options exist to safely address this imbalance, as sodium channel openers cannot restore it, and most I_To blockers are cardiotoxic. The selective blockade of I_To by 2Nal that we describe here helps restore the balance of electrical currents between I_To and I_Na. Our study presents a novel, safe partial antagonist of I_To that may help prevent arrhythmias associated with Brugada syndrome. Full article

Astringency in persimmon fruit is often eliminated by treatment with gaseous carbon dioxide, dry ice, or alcohol. However, these methods are time-consuming and labor-intensive, and astringency may recur after heat treatment. In this study, a method for easily reducing astringency was investigated by taking advantage of the benefits of combining proteins and polysaccharides. In the first experiment, the protein materials with strong astringency-reducing effects were screened from among 15 protein-rich foods using astringent persimmon juice (APJ), and collagen peptides were found to be highly effective. However, syneresis was observed when 1% collagen peptide powder was added to the astringent persimmon paste (AP). Therefore, in the second experiment, 0.5% collagen peptides (protein) were applied to reduce heating-induced astringency and reversion and 0.5% polysaccharides (guar, and xanthan gums) to maintain color and suppress syneresis. The results demonstrate that the combination of collagen peptide and polysaccharides is optimal for removing astringency in persimmon, inhibiting its recurrence by heating, and maintaining product quality. The results of this study may reduce the labor required for the astringency removal process, broaden the uses of AP, and facilitate the effective utilization of discarded astringent persimmons that do not meet the standards. Full article