Search Results (881)

Background: The pathophysiological mechanisms of Abdominal Aortic Aneurysm (AAA) are not elucidated. Alterations in mitochondrial function, such as a reduction in oxidative phosphorylation (OXPHOS), have been observed at genome level and functionally in vascular smooth muscle cells. Metformin reduces AAA development and growth in diabetic patients, but the precise mechanisms are not known. In this paper we aim to demonstrate the feasibility of measuring mitochondrial functional capacity ex vivo in intact murine aneurysmal tissue and confirm a decrease in OXPHOS, and to determine if the protective effect of metformin on AAA is mediated by mitochondrial function. Methods: AAA was induced in ApoE KO mice by administration of angII (1000 ng/kg/min) through osmotic minipumps. Metformin was administered in drinking water at a dose of 100 mg/kg/day. The abdominal aorta was isolated in situ and mitochondrial functional capacity was analyzed ex vivo in whole permeabilized tissue by high-resolution respirometry. Results: Mitochondrial respiration was successfully measured ex vivo in whole aneurysmal tissue. Mitochondrial function was impaired in angII-treated mice, with decreased fold change in Complex I and Complex I+II oxygen consumption, relative to basal levels. Complex II oxygen consumption was also decreased in angII-treated mice. Rescue treatment of mice with metformin did not affect or restore mitochondrial function. Conclusions: Mitochondrial function can be evaluated in murine whole aneurysmal tissue, providing a method for a physiological approach to the study of mitochondrial function in AAA. Mitochondrial function is impaired in AAA. However, rescue treatment with metformin is not sufficient to recover mitochondrial function and seems not to be the mechanism behind prevention of aneurysm. Full article

Background: The aim of our study was to evaluate the association of angiopoietin 2 (ANGPT2) rs2442598 and vascular endothelial growth factor A (VEGFA) rs2010963 with diabetic nephropathy (DN) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Angiopoietin–endothelial tyrosine kinase receptor (Ang-Tie2) and VEGF-A signaling regulate glomerular endothelial stability and permeability and may contribute to DN susceptibility. Methods: We conducted a case–control study including 897 unrelated Slovenian subjects with T2DM (344 DN cases; 553 long-standing T2DM controls without DN). ANGPT2 rs2442598 and VEGFA rs2010963 were genotyped using TaqMan assays. Genetic associations were analysed using co-dominant, additive, dominant, and recessive genetic models with logistic regression adjusted for waist circumference, systolic blood pressure, fasting glucose, and triglycerides. Results: ANGPT2 rs2442598 was significantly associated with DN, with increased risk in carriers of the C allele, including a significant additive per allele effect (OR 1.39, 95% CI 1.10–1.74) and a dominant model effect (OR 1.47, 95% CI 1.11–1.96). In contrast, VEGFA rs2010963 showed no evidence of association across genetic models. Conclusions: In Slovenian patients with T2DM, ANGPT2 rs2442598 is associated with DN, whereas VEGFA rs2010963 is not. This association suggests that ANGPT2 genetic variation may influence DN risk and supports further functional work to define the biological effects of rs2442598. Full article

Background: Transarterial chemoembolization (TACE) is an established image-guided, minimally invasive therapy for unresectable hepatocellular carcinoma (HCC). However, post-embolization hypoxia often triggers compensatory angiogenesis and an immunosuppressive microenvironment, limiting long-term efficacy. We hypothesized that the immediate image-guided hepatic arterial infusion (HAI) of a PD-1 inhibitor following TACE could synergistically enhance local tumor control. Methods: In this retrospective, propensity-score-matched study, 226 patients with unresectable HCC (January 2021–June 2024) were analyzed. After 1:1 matching, 84 pairs were included: Study Group (TACE + HAI-nivolumab) and Control Group (TACE alone). Nivolumab (3 mg/kg) was infused via the hepatic artery under fluoroscopic guidance immediately after embolization. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR) by mRECIST and changes in serum angiogenesis/immune biomarkers. Results: The Study Group demonstrated significantly longer median OS (16.2 vs. 12.8 months; HR 0.62, 95% CI: 0.44–0.88, p = 0.007) and median PFS (9.8 vs. 6.5 months; p < 0.001). ORR was higher with combination therapy (58.3% vs. 36.9%, p = 0.006). Mechanistically, HAI-nivolumab suppressed the post-TACE surge in VEGF and Ang-2 (p < 0.001) and increased the peripheral CD4+/CD8+ T-cell ratio. Grade 3/4 adverse events were comparable between groups (14.3% vs. 10.7%, p = 0.485). Conclusions: The image-guided combination of TACE with immediate HAI of nivolumab is associated with improved survival and tumor response in unresectable HCC. This strategy may counteract the adverse post-embolization microenvironment by simultaneously inhibiting angiogenesis and reactivating local immunity, representing an advanced image-guided combination therapy with strong translational relevance. Full article

Autoimmune thyroid diseases (AITD) are based on reactivity to thyroid self-antigens, resulting in varying degrees of persistent inflammation and glandular hyperplasia. The aim of this study was to investigate the interplay between angiogenesis, inflammation, and oxidative stress in patients with AITD. The study included patients with AITD, divided into a group with Hashimoto’s thyroiditis (HT) and a group with Graves’ disease (GD), as well as healthy controls. The results showed that subjects with GD had significantly higher concentrations of angiopoietin-2 (Ang-2) compared to those with HT and the healthy controls (p < 0.001). Inflammatory parameters (C-reactive protein (CRP), the systemic inflammatory immune response index (SII), and the CRP/albumin ratio (CRP/alb)) were higher in both AITD groups (p < 0.001). Oxidative stress parameters were more pronounced in AITD, while the activity of antioxidant enzymes was reduced. Ang-2 positively correlated with H₂O₂ (r = 0.394, p = 0.006) and NO (r = 0.519, p = 0.001) in HT, as well as with O₂⁻ (r = 0.232, p = 0.009) and TBARS (r = 0.190, p = 0.038) in GD, while in GD it showed a negative correlation with SOD (r = −0.426, p = 0.012) and CAT (r = −0.534, p = 0.008). Thus, angiogenesis, inflammation, and oxidative stress are interconnected processes in AITD, which may have significance for further understanding of the disease and the development of therapeutic approaches. Full article

Background: Abdominal aortic aneurysm (AAA) is a vascular disease with a high mortality rate upon rupture (85–90%). Surgical repair remains the most effective intervention, whereas pharmacological treatments to prevent aneurysm expansion or rupture are limited. Vascular smooth muscle cells (VSMCs) play a crucial role in AAA pathogenesis, and metabolic dysregulation is increasingly recognized as a contributor to disease progression. This study investigated metabolic changes in VSMCs and their association with AAA pathology using untargeted metabolomics. Methods: Angiotensin II (Ang II) was used to stimulate rat VSMCs and induce AAA in ApoE−/− mice. Untargeted metabolomic analysis was performed using liquid chromatography–tandem mass spectrometry to detect metabolite changes. Differential metabolites were identified using orthogonal partial least squares discriminant analysis, and metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes and metabolic set enrichment analysis. Results: In Ang II-treated VSMCs, 54 differential metabolites (24 upregulated; 30 downregulated) were identified, whereas 470 differential metabolites (206 upregulated; 264 downregulated) were detected in mouse aortas. Three metabolites—carnitine, lysophosphatidylcholine (0:0/20:4), and 5-hydroxyeicosatetraenoic acid—were common in both models and were enriched in bile secretion and tryptophan metabolism pathways. The carnitine–FXR signaling axis emerged as a potential therapeutic target. Conclusions: This study revealed Ang II-induced metabolic changes in VSMCs and their association with AAA pathology. The carnitine–FXR signaling axis may contribute to AAA development, providing new directions for diagnostic biomarkers and therapeutic targets. Future studies should validate these findings in human AAA samples to determine their clinical relevance. Full article

This study investigates the dynamics of a delayed fractional-order competition-competition-cooperative system with Beddington–DeAngelis functional responses. First, we prove the boundedness and uniqueness of the solutions. We analyze the existence conditions and local asymptotic stability of various equilibrium points using the stability theory. Second, by taking the competition time delay $\tau$ as the bifurcation parameter, we derive explicit criteria for the stability of the system and the onset of aHopf bifurcation. Once the delay surpasses a critical threshold, the system loses its stability and displays periodic oscillatory behavior. Furthermore, the influence of the fractional order on the system dynamics is also examined. Finally, numerical simulations are performed to verify the theoretical results, providing significant insights into ecosystem complexity. Full article

This paper presents a novel mathematical framework for anthrax transmission by integrating Caputo fractional derivatives, distributed delays, and a Beddington–DeAngelis incidence function. The proposed model captures memory effects in disease progression, temporal heterogeneities in pathogen release, and saturation phenomena in host–pathogen interactions. We establish the well-posedness of the system and derive the basic reproduction number ${\mathcal{R}}_0$, which serves as a sharp threshold for disease dynamics: when ${\mathcal{R}}_0\le 1$, the disease-free equilibrium is globally asymptotically stable; when ${\mathcal{R}}_0>1$, a unique endemic equilibrium emerges and is globally stable. Theoretical analysis demonstrates that the fractional order modulates convergence rates through memory effects, while distributed delays influence oscillatory behaviors and time to equilibrium. Numerical simulations validate these findings and illustrate the impacts of key parameters on disease transmission. The results provide a scientific foundation for designing targeted public health interventions in anthrax control. Full article

Acute myocardial infarction can lead to ventricular remodelling, which affects ventricular function and survival prognosis. Therefore, improving ventricular remodelling has become a focus of research. This study aims to investigate the effect of Acanthopanax senticosus leaf saponins (ASS) on cardiac function and left ventricular remodelling in a rat model of myocardial infarction, and explore its potential mechanism. Coronary artery ligation was used to establish a rat model of myocardial infarction, and ASS was administered orally for 28 days. After 28 days, cardiac function was evaluated by hemodynamic detection, and the levels of myocardial enzymes, inflammatory cytokines, oxidative stress and fibrosis-related factors were detected. The degree of fibrosis was evaluated by immunohistochemical detection of collagen I and collagen III deposition. The expression levels of MMP-2, MMP-9 and TIMP-1 were checked by Western blot. Compared with the Sham group, the cardiac function of the Model group was significantly impaired, and ASS administration could improve this change. In addition, compared with the Model group, ASS significantly alleviated myocardial injury, reduced the release of inflammatory cytokines TNF-α and IL-β, improved the oxidative stress state, reduced the release of NT-propBNP, Ang II, ET-1 and inhibited myocardial fibrosis. Moreover, ASS could reduce the expression of MMP-2 and MMP-9, and increase the expression level of TIMP-1. In conclusion, ASS may inhibit left ventricular remodelling by reducing the expression of MMP-2 and MMP-9. Full article

Landscape features often shape maternal genetic structure by influencing connectivity. In this study, habitat fragmentation, a major threat to the Asian elephant (Elephas maximus), was assessed through an integrated approach involving mitochondrial DNA (mtDNA), habitat-suitability modeling, and circuit-based landscape-resistance analyses. Two regions from Thailand, Phu Khieo (PK) and Khao Ang Rue Nai (ARN) Wildlife Sanctuaries, were investigated. Fourteen mtDNA haplotypes were identified among 66 samples, with relatively high diversity and population expansion in PK. Maternal genetic differentiation was identified between the PK and ARN groups. Environmental variables, such as urbanization and road proximity in ARN and topographic wetness and stream distance in PK, were associated with genetic distances, suggesting these features restricted female-mediated connectivity. Fine-scale spatial analysis revealed significant local genetic structure only in PK, whereas no autocorrelation was detected in ARN, suggesting potential impacts of fragmentation. Genetic landscape surfaces illustrated spatial heterogeneity, pinpointing isolation zones near high anthropogenic disturbance. These findings demonstrate that broad-scale models may overlook fine-scale patterns of maternal genetic isolation. Therefore, conservation strategies should incorporate spatially explicit analyses to identify and restore crucial movement corridors, particularly in fragmented regions like ARN, for promoting connectivity and population viability. Full article

Our previous studies have shown that continuous infusion of angiotensin II (Ang II) in C57BL/6J mice causes dysfunction and a cachexia-like pathogenesis in both skeletal muscle and the left ventricle, which is significantly reduced by withaferin A (WFA), a steroidal lactone. However, it remains unknown whether WFA can reverse right ventricular (RV) dysfunction induced by Ang II. To determine the effects of WFA in attenuating Ang II-induced RV dysfunction, we employed a model in which continuous Ang II infusion via an osmotic pump in C57BL/6J mice induced cardiac remodeling. We then focused on investigating RV performance and structural changes using echocardiography and histopathological examination, as well as quantitative real-time PCR (qRT-PCR) for mRNA expression. Echocardiographic analysis demonstrated that Ang II significantly increased RV wall thickness and impaired RV systolic and diastolic function, as indicated by reductions in tricuspid annular plane systolic excursion, TV E/E′ ratio, RV S′, and RVOT VTI. The qRT-PCR analysis revealed marked upregulation of pro-fibrotic markers, including TGF-β, fibronectin, and collagen. WFA treatment restored RV functions and significantly attenuated Ang II-induced RV dysfunction and fibrosis. Our findings provide the first evidence that WFA attenuates Ang II-induced cachexia-like remodeling and dysfunction of the RV. These results position WFA as a compelling therapeutic candidate for cardiac cachexia, offering direct anti-fibrotic and cardioprotective benefits that warrant further translational development. Full article

Background: Axonal misdirection remains a major limitation in peripheral nerve repair. While nerve guidance conduits (NGCs) and nerve scaffolds (NSCs) have advanced structurally, it is unclear whether these designs effectively reduce misdirection compared to autografts (ANGs). This systematic review evaluates the impact of NGC and NSC structural features on axonal dispersion and reinnervation accuracy using retrograde tracing animal models. Methods: A systematic search was performed through Medline (PubMed), Scopus (EBSCOhost), and the Cochrane Library from inception to December 2024. Eligible studies included mammalian in vivo models of peripheral nerve transection repaired by direct coaptation, autografts, or artificial conduits and assessed with retrograde axonal tracing. Data on neurons labeling, innervation accuracy, and histomorphometric parameters were extracted, and misdirection rates were calculated. Risk of bias was assessed using the SYRCLE tool. Due to heterogeneity, data were synthesized narratively following the SWiM framework. Results: Out of 4043 records identified through database searching and 37 through citation searching, 19 studies (49 experimental groups) met the inclusion criteria. Motoneuron counts were consistently reported across all arms, but no outcome assessing axonal misdirection was reported in more than half. Structured designs resulted in outcomes more closely aligned with ANG repair, while unstructured generally underperformed, and certainty of evidence was very low. Discussion: The evidence in this study was limited by high risk of bias, substantial inconsistency across heterogeneous study designs and outcomes, and imprecision from small animal models with sparse outcome measures. Despite the trend for structured designs to improve over basic hollow designs, current evidence does not support any structure as superior. Future research should be more standardized to provide reliable knowledge translational into clinical practice. Full article

This paper introduces SIDe-HBIM (Single-Image Depth inference for HBIM), a semi-automated image-to-BIM pipeline aimed at improving the integration of architectural decorative elements into HBIM environments. The research addresses the difficulty of representing geometrically complex yet information-oriented heritage components when traditional survey techniques are impractical or disproportionate. Starting from a single photographic input, the methodology combines AI-based depth estimation, quantitative computational evaluation and parametric modeling to generate lightweight, morphologically coherent 3D elements suitable for non-photorealistic HBIM applications. Multiple image-to-depth models are processed in parallel and ranked through a weighted synthetic index based on geometric and structural indicators, after which the selected depthmap is converted into a continuous NURBS surface and integrated into a BIM environment. Application to three heterogeneous case studies from the Basilica of Santa Maria degli Angeli (Assisi) demonstrates that SIDe-HBIM is particularly effective for bas-reliefs and moderate-relief decorative apparatuses, offering a reproducible and efficient alternative for HBIM-oriented documentation. Full article

Introduction: The pro-inflammatory cytokine interleukin-17A (IL-17A) has a key role in the inflammatory cascade and promotes vascular inflammation and dysfunction. In addition, IL-17A is centrally involved in several autoimmune diseases. IL-17A deficiency has been linked to reduced vascular inflammation associated with attenuated arterial hypertension under long-term angiotensin II (Ang II) exposure for four weeks. This is of interest as IL-17A is one factor linking several autoimmune diseases with cardiovascular comorbidity. So far, little is known about the effects of IL-17A during the early stages of vascular dysfunction development—an interval possibly representing an optimal therapeutic window. Methods: Mice lacking the IL-17A receptor alpha (IL-17RAdel) and wild-type counterparts were treated with Ang II for one week (1 mg/kg bodyweight/week). We assessed systemic oxidative stress formation and vascular function, as well as inflammatory cells in the vessel wall. In parallel, C57BL/6J mice treated with Ang II received anti-IL-17A therapy, to evaluate the same parameters. Results: Both IL-17RA-deficient mice and anti-IL-17A-treated C57BL/6J mice exhibited an attenuated oxidative stress response and mitigated vascular inflammation following one week of Ang II treatment. These effects did not significantly prevent the onset of Ang II-induced vascular dysfunction at that timepoint. Conclusions: After one week of Ang II treatment, antagonizing IL-17RA or IL-17A only partially reduced/attenuated the Ang II-induced effects on the vasculature. In the context of IL-17A-driven autoimmune diseases with associated vascular pathology, our findings suggest that anti-inflammatory therapies alone may not be sufficient to attenuate vascular impairment. A combined approach including agents with direct protective vascular effects may be required for effective intervention for the associated vascular comorbidity. Full article

Sustainable service excellence in globalized industries requires organizations to develop workforce capabilities that support long-term relationship-building, cultural respect, and effective cross-cultural communication. This study examines how cultural intelligence functions as a mechanism for sustainable cross-cultural workforce development by investigating relationships among individual cultural values, cultural intelligence dimensions, and influence tactics among airline cabin crew members. Integrating Hofstede’s cultural dimensions framework, Ang and colleagues’ cultural intelligence model, and Yukl’s influence tactics taxonomy, we test a comprehensive mediation model using survey data from six hundred and sixty-three cabin crew members employed by international airlines operating in Turkey. The findings reveal that collectivism, long-term orientation, and uncertainty avoidance positively predict cultural intelligence development, creating foundations for sustainable cross-cultural competence. Cultural intelligence dimensions demonstrate differentiated effects on influence tactics, with metacognitive and behavioral cultural intelligence enhancing rational persuasion, behavioral cultural intelligence exclusively predicting relational tactics, and complex competitive mediation patterns for coercive tactics wherein motivational cultural intelligence reduces pressure-based influence while cognitive and behavioral dimensions increase strategic assertiveness. Cultural values directly influence tactics beyond cultural intelligence effects, with uncertainty avoidance most strongly predicting both rational and relational approaches that support relationship sustainability, while masculinity and power distance drive coercive tactics that may undermine long-term service relationships. These findings demonstrate that cultural intelligence functions as a multidimensional mediating mechanism with sometimes opposing effects, challenging assumptions that cross-cultural competencies uniformly produce sustainable outcomes. The research contributes to sustainable human resource management theory by illuminating how cultural socialization influences behavioral outcomes through complex psychological pathways, while offering practical guidance for aviation industry recruitment, training, and performance management systems seeking to build sustainable cross-cultural service capabilities. By revealing that certain cultural intelligence dimensions can enable both relationship-building and strategic coercion, the study highlights the importance of coupling cross-cultural skill development with ethical frameworks and motivational engagement to ensure that enhanced cultural capabilities support rather than undermine sustainable, respectful cross-cultural service relationships. Full article

This study explores the feasibility of introducing Gregorian chant into contemporary Chinese Methodist worship in Malaysia. Using ethnographic methods including participant observation, interviews, and focus groups, this article documents a pilot study conducted at Sing Ang Tong Methodist Church in Sibu, Sarawak, where seven singers learned and performed the communion chant Gustate et videte. Three different transcription editions were created to bridge the gap between medieval square notation and modern Western notation, which is more familiar to the participants. The chant was translated into Chinese alongside the original Latin text. The majority preferred the quaver-crotchet notation edition and supported performing the chant in both Latin and Chinese to balance authenticity with accessibility. Participants found the modal melodic structure and free rhythm challenging initially but developed appreciation for the chant’s meditative qualities. The performance during Holy Communion services in October 2022 received mixed congregational responses, with many describing it as creating a “calm and prayerful atmosphere” while some expressed discomfort with the unfamiliar musical style. The study demonstrates that Gregorian chant can be successfully integrated into Chinese Methodist worship contexts, particularly during solemn liturgical occasions, when approached with appropriate liturgical sensitivity and cultural adaptation. Full article