Search Results (209)

In recent years, imaginative techniques have effectively addressed the growing demand for brief, evidence-based treatments applicable in various contexts. Among these, Imagery with Rescripting (ImRs) was developed within the Schema Therapy model. ImRs can be applied individually or in combination with other protocols, demonstrating significant outcomes even after just one session. This narrative review aims to provide an overview of the applications of ImRs, with a specific focus on its effectiveness in trauma-related disorders. The search string used was “(‘imagery with Rescripting’) AND ((‘Trauma’ OR ‘PTSD’ OR ‘dissociation’))”. The following databases were utilized: PubMed, Scopus, Web of Science, Medline, Embase, and PsychInfo. The research included English-language and Italian-language studies, encompassing experimental and observational designs, case reports, and case series. Samples consisted of healthy participants or clinical populations aged 18 years and older, with no temporal limitations. A total of 56 articles were selected. The results highlight the efficacy of this intervention, whether administered individually or as part of combined protocols, across a wide range of diagnostic categories, including healthy samples, post-traumatic stress disorder (PTSD), borderline personality disorder (BDP), sleep disorders, psychotic spectrum disorders, chronic pain, anxiety disorders, depression, and eating disorders. The studies also support hypotheses about the mechanisms underlying the technique: ImRs facilitates the reprocessing of the meaning associated with mental representations and reduces the occurrence of negative intrusive images related to past events. This process alters and rewrites the individual’s negative memories and images. The narrative review supports the effectiveness of ImRs in treating various psychopathological disorders, both trauma-related and non-trauma-related. In addition to highlighting the effectiveness of ImRs when appropriately integrated with other techniques, the review emphasizes the importance of conducting efficacy studies on larger samples to evaluate ImRs as a standalone intervention model. Full article

A significant proportion of patients undergoing invasive coronary angiography for angina have no obstructive coronary artery disease (CAD). In such patients, coronary microvascular dysfunction (CMD) and vasospastic angina (VSA) represent key pathophysiological mechanisms. We report a case of a 58-year-old male with exertional chest pain and exercise ECG changes typical of left main or multivessel CAD. Coronary computed tomography angiography (CCTA) showed borderline stenosis of the distal left main coronary artery. Coronary angiography revealed no critical stenosis. A comprehensive functional assessment demonstrated reduced coronary flow reserve (CFR = 2.0) and an elevated index of microcirculatory resistance (IMR = 25), consistent with CMD. An intracoronary acetylcholine provocation test induced severe focal vasospasm of the mid-left anterior descending artery (LAD) with ST-segment elevation and anginal pain, promptly relieved by nitroglycerin, confirming VSA. This case highlights the diagnostic and clinical importance of invasive functional testing in patients with angina and non-obstructive coronary arteries (ANOCA/INOCA). The coexistence of CMD and VSA (two distinct but overlapping pathophysiological endotypes) is increasingly recognized as a marker of adverse prognosis. Functional coronary assessment should be considered in all patients with angina and non-obstructive coronary arteries, as identifying mixed endotypes enables precise, mechanism-guided therapy. Full article

Alzheimer’s disease (AD) is a catastrophic neurodegenerative disorder marked by progressive decline of cognitive function, memory loss, and neuronal death. Its pathology is characterized by the formation of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles from tau hyperphosphorylation. Despite extensive research, current treatments are limited to symptomatic relief and are associated with significant side effects. This accentuates the critical need for alternative therapeutic strategies with potent neuroprotective effects and minimal toxicity. This study investigates the neuroprotective potential of glycyrrhizic acid, as the precise molecular mechanisms by which it might improve AD pathology remain poorly understood. Using an Aβ₄₂-induced IMR-32 cell model of AD, our research revealed that Aβ₄₂ treatment caused significant protein alterations associated with AD pathology, mitochondrial dysfunction, cell cycle re-entry, and synaptic activity. Co-treatment with glycyrrhizic acid not only restored these protein levels, but also mitigated the hyperactivation of several key signaling pathways and rescued neurons from apoptosis. These findings suggest that glycyrrhizic acid exerts neuroprotective effects by preventing mitochondrial dysfunction and apoptosis via modulation of critical signaling pathways. This study provides strong evidence for glycyrrhizic acid’s neuroprotective properties in AD, paving the way for further research into its potential as a promising therapeutic agent for Alzheimer’s disease. Full article

Advances in multimodal therapy for high-risk neuroblastomas (NBs) have plateaued, prompting therapeutic initiatives to harness the immune system. NBs, however, are immunologically “cold” and a significant challenge to immunotherapy. Here, in a Jurkat lymphocyte cytotoxicity model, we describe an antigen-independent, cell-mediated mechanism for eliminating NB cells, first detected in PMA-activated low pcDNA-SH-SY5Y and high TrkAIII-SH-SY5Y TrkAIII-expressing cells, which are resistant to Jurkat elimination under normal conditions. Characterization of this mechanism through live cell imaging, adhesion assays, RT-PCR, Western blotting and indirect IF, employing a variety of inhibitors, indicates that it initiates with PMA-induced NB cell CCL2 expression. This results in CCL2 promotion of Jurkat CCR2b expression, CCL2/CCR2b-mediated Jurkat LFA-1 activation and the formation of cytotoxic lipid-raft LFA1/ICAM-1 immune synapses, through which Jurkat m-TRAIL combines with PMA-enhanced NB cell DR5/TRAIL-R2 expression to induce NB cell apoptosis. This mechanism is enhanced by the NB-associated oncoprotein TrkAIII through Shp/Src-regulated c-FLIP sequester and is PD-L1/PD-1-independent and resistant to osteoprotegerin. It eliminates both non-MYCN-amplified (SH-SY5Y and SK-N-SH) and MYCN-amplified (SMS-KCNR) NB cells that exhibit PMA-inducible CCL2 expression but not MYCN-amplified NB cells (IMR-32 and NB-1) that exhibit CCL2 repression, and is offset by reciprocal NB cell-induced Fas-mediated Jurkat cell apoptosis. These findings form a solid foundation for further pre-clinical development aimed at identifying clinically relevant physiological immune cell equivalents and alternative PKC activators, with the ultimate goal of translating this mechanism into an effective immune-therapeutic approach for the treatment of high-risk non-immunogenic NBs, especially NBs that exhibit CCL2 and TrkAIII expression. Full article

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines. Full article

Inflammatory bowel disease (IBD) arises from chronic dysregulation at the epithelial–stromal interface, creating a need for in vitro systems that better capture these interactions. In this study, we developed a 3D co-culture platform in which HT-29 intestinal epithelial cells and IMR-90 fibroblasts are embedded within an alginate–gelatin hydrogel, alongside a complementary interface model using a plasma-treated electrospun mesh to spatially compartmentalize stromal and epithelial layers. We first assessed metabolic activity, viability, and proliferation across several epithelial-to-fibroblast ratios and identified 1:0.5 as the most supportive of epithelial expansion. The A1G7 hydrogel maintained high viability (>92%) and sustained growth in all mono- and co-cultures. To evaluate inflammatory competence, models were stimulated with lipopolysaccharide (LPS), administered either within the hydrogel or through the culture medium. LPS exposure increased TNF-α and IL-1β secretion in both configurations, with the magnitude of the response depending on the delivery route. Treatment with dexamethasone consistently reduced cytokine levels, confirming the model’s suitability for pharmacological testing. Together, these results demonstrate that the alginate–gelatin system provides a reproducible epithelial–stromal platform with quantifiable inflammatory readouts, offering a practical foundation for mechanistic studies and early-stage screening of anti-inflammatory therapeutics in IBD. Full article

Multimodal imaging plays a central role in optimizing the evaluation and management of myocardial ischemia by leveraging the complementary strengths of echocardiography, cardiac magnetic resonance imaging (CMR), single photon emission computed tomography (SPECT), positron emission tomography (PET), and invasive coronary angiography (ICA). Noninvasive functional imaging is typically recommended for patients with intermediate to high pre-test probability of coronary artery disease, while coronary computed tomography angiography (CCTA) is preferred for low to intermediate risk. Stress echocardiography is valuable for detecting wall motion abnormalities and is particularly effective in multivessel or left main disease, where perfusion techniques may miss balanced ischemia. CMR offers high spatial resolution and quantitative assessment of myocardial blood flow (MBF), while SPECT and PET quantify ischemic burden, with PET providing superior accuracy for MBF and microvascular disease. ICA remains the gold standard for defining the presence, location, and severity of epicardial coronary stenosis. It is indicated when noninvasive imaging reveals high-risk features, when symptoms are refractory to medical therapy, or when noninvasive results are inconclusive. While ICA offers high spatial resolution, it alone cannot assess the hemodynamic significance of intermediate lesions, nor the coronary microvasculature. Adjunctive invasive hemodynamic and provocative coronary testing (e.g., Fractional Flow Reserve—FFR, invasive Coronary Flow Reserve—CFR, Index of Microcirculatory Resistance—IMR, acetylcholine test) provide essential insights, especially in ischemia with nonobstructive coronary arteries. Given its procedural risks, ICA should be reserved for cases where it will impact management. Intravascular imaging may be used to further characterize lesions. In summary, modality selection should be individualized based on patient characteristics, comorbidities, contraindications, and the need for anatomical versus physiological data. Integrating noninvasive and invasive modalities provides a comprehensive, patient-centered approach to ischemia evaluation. Full article

Background: Patient-reported outcomes are integral to chronic coronary syndrome (CCS) care. The Seattle Angina Questionnaire (SAQ) is validated and prognostic, yet its clinical integration in Bulgaria is undefined. Aim: The aim of this study was to provide a structured, clinically oriented framework for integrating the SAQ into the full CCS care pathway—from screening and phenotyping (obstructive vs. ANOCA/INOCA endotypes) to diagnostics, mechanism-tailored therapy, and follow-up—while outlining a pragmatic roadmap for Bulgarian implementation. Methods: We conducted a semi-structured narrative review (1995–2024) of SAQ’s validation, prognostic utility, and implementation in the literature, augmented with guideline-based frameworks for CCS/ANOCA care. Results: The SAQ (and SAQ-7) shows strong reliability and responsiveness and independently predicts health status and clinical outcomes. Embedding the SAQ at baseline, at 4–12 weeks after therapy changes, and after 6–12 months enables symptom-guided decision-making. A phenotype-guided pathway is proposed that couples the SAQ with CAD burden assessment and—where indicated—ANOCA diagnostics (CFR/IMR, vasoreactivity testing). Mechanism-tailored therapy maps to endotypes (e.g., VSA → CCB ± nitrates; MVA → beta-blocker/ACEi/statin ± ranolazine; obstructive CADGDMT ± PCI/CABG). A minimum dataset, metrics, and registry fields are specified for Bulgarian deployment. Conclusions: A clinically structured framework clarifies how the SAQ adds value beyond description—by informing triage, treatment selection, and follow-up across CCS phenotypes. This approach provides educational guidance and a practical blueprint for pilot implementation in Bulgaria. Full article

Objectives: This exploratory preclinical study aimed to compare the correlations of apparent diffusion coefficient (ADC) and native T1 mapping histogram features with tumor cell proliferation, microvessel density (MVD), and extracellular matrix composition in neuroblastoma xenografts. Methods: Neuroblastoma xenografts (n = 42) were established by subcutaneously injecting three MYCN-amplified/non-amplified human neuroblastoma cell lines (IMR-32, SK-N-BE(2), and SH-SY5Y; n = 14 per group) into female immunodeficient BALB/c-nude mice. Once tumors reached a diameter within the range of 12–15 mm, native T1 mapping and diffusion-weighted imaging were performed using a 3.0T clinical MRI scanner. Tumor cell proliferation and MVD were assessed via immunohistochemical Ki-67 staining and CD31 staining, respectively. Collagen fibers were visualized using Masson staining to calculate the collagen volume fraction (CVF). Pearson correlation coefficients with false discovery rate (FDR) correction were used to evaluate their associations. Results: Significant negative correlations were observed between Ki-67 expression and multiple ADC values after FDR correction, including ADC_10Percentile (r = −0.397, adjusted p = 0.032), ADC_90Percentile (r = −0.394, adjusted p = 0.032), ADC_maximum (r = −0.362, adjusted p = 0.048), ADC_mean (r = −0.421, adjusted p = 0.032), ADC_median (r = −0.422, adjusted p = 0.032), ADC_minimum (r = −0.390, adjusted p = 0.032), and ADC_{rootmeansquared} (r = −0.419, adjusted p = 0.032). In contrast, multiple T1 mapping features showed significant positive correlations with CVF (adjusted p < 0.05). Conclusions: ADC and T1 mapping provide complementary insights into tumor proliferation and extracellular matrix composition in neuroblastoma. These preclinical findings support further research to validate their potential clinical utility. Full article

Background/objectives: Cellular senescence is a hallmark of aging that contributes to tissue dysfunction and age-related diseases. This process is characterized by the activation of the cyclin-dependent kinase inhibitor p16^INK4A and the secretion of pro-inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). In this study, we used human lung-derived cells, including A549 and IMR90 fibroblasts, to identify bioactive compounds from the roots of Liquidambar formosana that suppress p16^INK4A activity and attenuate SASP expression. Methods: Bioactivity-guided isolation was performed to obtain target compounds. The structures of the new compounds were elucidated using extensive 1D and 2D NMR spectroscopic analyses as well as high-resolution mass spectrometry. All isolated compounds were evaluated for their ability to inhibit p16^INK4A, a key regulator of the cell cycle and an important tumor suppressor protein. Results: Two previously undescribed monoterpenoids (1 and 2), characterized as cinnamic acid esters with a monoterpene-derived core, were isolated from the roots of L. formosana, along with six known compounds (3–8). Notably, compound 3 exhibited promising inhibition of p16^INK4A with an IC₅₀ value of 3.9 μM. Furthermore, this compound attenuated the senescence phenotype, as demonstrated by β-galactosidase staining and RT-qPCR analysis. This represents the first report identifying bioactive monoterpenoids from L. formosana that inhibit aging-related biomarkers such as p16^INK4A. Conclusions: These results suggest that cinnamic acid-conjugated monoterpenoids may serve as interesting lead structures for the development of agents targeting the p16^INK4A pathway for the treatment of aging-associated diseases. Further studies will be required to clarify the mechanisms of action of this compound and to evaluate its in vivo efficacy. Full article

Background/Objectives: The accumulation of Nε-carboxymethyllysine (CML), a major advanced glycation end product (AGE), has been implicated in neuronal dysfunction by promoting oxidative stress, endoplasmic reticulum (ER) stress, and dysregulation of amyloid-β (Aβ) metabolism. This study evaluated the neuroprotective properties of coixol, a naturally occurring polyphenolic compound derived from the outer layers of Coix lacryma-jobi L. var. ma-yuen, in a CML-induced injury model using IMR-32 human neuronal-like cells. Methods: Cells were pretreated with coixol (1 μmol/L), N-acetyl-L-cysteine (NALC, 1 mmol/L), or 4-phenylbutyric acid (4-PBA, 200 μmol/L) for 1 h prior to CML (100 μmol/L) exposure for 24 h. Cell viability was determined by colorimetric analysis of 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide, while intracellular reactive oxygen species (ROS) generation was quantified using a fluorescence-based oxidative stress probe. Activities of key antioxidant enzymes and caspase-3 were determined using commercial assay kits. The expression of Aβ isoforms, amyloidogenic enzymes, ER stress markers, and apoptosis-related signaling proteins was quantified through validated immunoassays. Results: Coixol pretreatment significantly enhanced cell viability by attenuating ROS accumulation and restoring antioxidant enzyme activities. Concurrently, coixol suppressed ER stress signaling via downregulation of the protein kinase R-like ER kinase/C/EBP homologous protein axis and modulated apoptosis by increasing B-cell lymphoma (Bcl)-2, reducing Bcl-2-associated X protein expression, and inhibiting caspase-3 activation and DNA fragmentation. Furthermore, coixol regulated Aβ metabolism by inhibiting the expression of β-site amyloid precursor protein-cleaving enzyme 1 and presenilin 1, while restoring insulin-degrading enzyme and neprilysin levels, leading to reduced accumulation of Aβ40 and Aβ42. Conclusions: Compared to NALC and 4-PBA, coixol demonstrated comparable or superior modulation across multiple pathological pathways. These findings highlight coixol’s potential as a neuroprotective candidate in AGE-associated neurodegenerative conditions. Full article

Objective: The objective of this study was to compare the performance and robustness of a deep learning reconstruction method against established alternatives for soft tissue CT image reconstruction. Materials and Methods: Images were generated from portal venous phase chest–abdomen–pelvis CT scans (n = 99) acquired on a dual-layer spectral detector CT using filtered back projection, iterative model reconstruction (IMR), and deep learning reconstruction (DLR) with three parameter settings, namely ‘standard’, ‘sharper’, and ‘smoother’. Experienced raters performed a quantitative assessment by considering attenuation stability and image noise levels in ten representative structures across all reconstruction methods, as well as a qualitative assessment using a four-point Likert scale (1 = poor, 2 = fair, 3 = good, 4 = excellent) for their overall perception of ‘smoother’ DLR and IMR images. One scan was excluded due to cachexia, which limited the quantitative measurements. Results: The inter-rater reliability for quantitative measurements ranged from moderate to excellent (r = 0.63–0.96). Attenuation values did not differ significantly between reconstruction methods except for DLR against IMR in the psoas muscle (mean + 3.0 HU, p < 0.001). Image noise levels differed significantly between reconstruction methods for all structures (all p < 0.001) and were lower than FBP with any DLR parameter setting. Image noise levels with ‘smoother’ DLR were predominantly lower than or equal to IMR, while they were higher with ‘standard’ DLR and ‘sharper’ DLR. The ‘smoother’ DLR images received a higher mean rating for overall image quality than the IMR images (3.7 vs. 2.3, p < 0.001). Conclusions: ‘Smoother’ DLR images were perceived by experienced readers as having improved quality compared to FBP and IMR while also exhibiting objectively lower or equivalent noise levels. Full article

Enhancer–promoter interactions (EPIs) play a key role in epigenetic regulation of gene expression, dominating cellular identity and functional diversity. Dissecting these interactions is crucial for understanding transcriptional regulatory networks and their significance in cell differentiation, development, and disease. Here, we propose a novel deep learning framework, EPIFBMC (Enhancer-Promoter Interaction prediction with FBMC network) that leverages DNA sequence and genomic features for accurate EPI prediction. The FBMC network consists of three key modules: the Four-Encoding module first encodes the DNA sequence in multiple dimensions to extract key sequence information; then the BESL (Balanced Ensemble Subset Learning) adopts an integrated subset learning strategy to optimize the feature-learning process of positive and negative samples; finally, the MCANet module completes the training of EPI prediction based on a Multi-channel Network. We evaluated EPIFBMC on three cell line datasets (HeLa, IMR90, and NHEK), and validated its generalizability across three independent datasets (K562, GM12878, HUVEC) through cross-cell-line experiments, comparing favorably with state-of-the-art methods. Notably, EPIFBMC balances genomic feature richness and computational complexity, significantly accelerating training speed. Ablation studies identified two key DNA sequence features—positional conservation and positional specificity score—which showed critical predictive value across a benchmark dataset of six diverse cell lines. The computational testing show that EPIFBMC shows excellent performance in the EPI prediction task, providing a powerful tool for decoding gene regulatory networks. It is believed that it will have important application prospects in developmental biology, disease mechanism research, and therapeutic target discovery. Full article

Inspection, maintenance, and repair (IMR) operations on underwater infrastructure remain costly and time-intensive because fully teleoperated remote operated vehicle s(ROVs) lack the range and dexterity necessary for precise cooperative underwater manipulation, and the alternative of using professional divers is ruled out due to the risk involved. This work presents and experimentally validates an autonomous, dual-I-AUV (Intervention–Autonomous Underwater Vehicle) system capable of assembling rigid pipeline segments through coordinated actions in a confined underwater workspace. The first I-AUV is a Girona 500 (4-DoF vehicle motion, pitch and roll stable) fitted with multiple payload cameras and a 6-DoF Reach Bravo 7 arm, giving the vehicle 10 total DoF. The second I-AUV is a BlueROV2 Heavy equipped with a Reach Alpha 5 arm, likewise yielding 10 DoF. The workflow comprises (i) detection and grasping of a coupler pipe section, (ii) synchronized teleoperation to an assembly start pose, and (iii) assembly using a kinematic controller that exploits the Girona 500’s full 10 DoF, while the BlueROV2 holds position and orientation to stabilize the workspace. Validation took place in a 12 m × 8 m × 5 m water tank. Results show that the paired I-AUVs can autonomously perform precision pipeline assembly in real water conditions, representing a significant step toward fully automated subsea construction and maintenance. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article