Search Results (16,442)

Marek’s disease (MD), caused by the oncogenic Marek’s disease virus (MDV), is a highly contagious avian infection that induces lymphoproliferative tumors. The RNA-binding protein ELAVL1 is known to regulate tumor cell proliferation and apoptosis, but its role in MDV-induced oncogenesis remains unclear. This study investigated whether ELAVL1 modulates proliferation and apoptosis in the MDV-transformed MSB1 cell line and whether its effects involve the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway. MSB1 cells were transiently transfected with ELAVL1-overexpressing plasmids (pEGFP-C-ELAVL1) or ELAVL1-specific siRNA, with expression confirmed by real-time PCR (qRT-PCR). Cell proliferation was assessed using the CCK-8 assay, while cell cycle distribution and apoptosis rates were analyzed by flow cytometry. COX-2 and PGE2 expression levels were determined by qRT-PCR, Western blotting, and ELISA. Overexpression of ELAVL1 significantly promoted the proliferation of MSB1 cells, decreased transition into the G1 phase, increased the proportions of S and G2 phase cells, and suppressed apoptosis. Correspondingly, both mRNA and protein levels of COX-2 and PGE2 were significantly elevated. Conversely, ELAVL1 knockdown significantly inhibited proliferation, induced G1 phase arrest, decreased S phase cells, and significantly decreased COX-2 and PGE2 expression. These findings indicate that ELAVL1 promotes proliferation and inhibits apoptosis in MDV-transformed MSB1 cells, potentially via the COX-2/PGE2 signaling pathway. Full article

Background/Objectives: This study aimed to assess the safety and efficacy of lung surgery for the treatment of early-stage non-small cell lung cancer (NSCLC) in octogenarians, with a specific focus on the Uniportal-VATS approach, evaluating surgical outcomes and short-term oncological results within a precision medicine perspective. Methods: This retrospective, single-center study included octogenarian patients who underwent surgical treatment for early-stage NSCLC between January 2018 and March 2024. Among 1329 patients treated during the study period, 136 octogenarians were carefully evaluated by a multidisciplinary board and selected for surgical management. Results: The mean age was 82.41 ± 2.72 years, with a prevalence of men (63.2%). In 107 (78.7%) cases, lung resection was performed using the Uniportal-video-assisted thoracic surgery (U-VATS) approach. Overall, 71 lobectomies (52.2%) and 65 segmentectomies or wedge resections (47.8%) were performed, balancing oncological radicality with comorbidities. Only minor complications occurred, such as atelectasis (2.9%), atrial fibrillation (4.4%), pneumonia (1.5%), or air-leakage (2.2%). Factors significantly associated with postoperative complications included open approach (p = 0.014), lobectomy as the extent of resection (p = 0.008), and chronic obstructive pulmonary disease (COPD) (p = 0.010). On multivariable analysis, lobectomy remained the only independent predictor for postoperative complications (OR: 5.95, 95% CI [1.24–28.62], p = 0.026). In-hospital and 90-day mortality were null. The median length of hospital stay in octogenarians was 6 days and was significantly shorter in the Uniportal-VATS group compared with the open surgery one (p < 0.001). All patients were discharged home independently. One- and three-year overall survival rates were 88% and 71%, respectively. No risk factor was associated with mortality in our series. Conclusions: Lung surgery, particularly the Uniportal-VATS approach, appears to be a safe and effective treatment option for octogenarian patients with early-stage NSCLC, provided that patient selection is carefully based on individual clinical characteristics within a multidisciplinary framework based on individualized risk stratification. When feasible, sublobar resection should be preferred in order to minimize postoperative complications. Full article

Background/Objectives: Dynamic remodeling of the zona pellucida (ZP) is a fundamental biochemical and structural process during human preimplantation development; however, its quantitative characterization and clinical relevance remain incompletely defined. The objective of this study was to evaluate dynamic ZP thinning as a functional marker of embryo developmental competence and to examine its relationship with follicular fluid (FF) biomarkers and clinical pregnancy. Methods: This prospective observational study included 47 IVF cycles performed at a single center, yielding 64 transferred blastocysts with complete time-lapse data. ZP thickness was measured from fertilization to 120 h post-fertilization using time-lapse imaging. Two quantitative parameters were derived: the relative thinning ratio (Δrel) and the linear thinning rate (slope). FF concentrations of growth differentiation factor 9 (GDF-9), hyaluronic acid (HA), and syndecan-4 (Syn4) were quantified by ELISA. Embryo-level associations with spontaneous blastocyst hatching were assessed using logistic regression and multivariate analyses, while patient-level models evaluated predictors of clinical pregnancy. Results: Embryos that underwent spontaneous hatching exhibited significantly greater Δrel than non-hatching embryos (p < 0.001). Δrel remained the strongest predictor of hatching in multivariable models (AUC = 0.91). Among FF biomarkers, only GDF-9 showed a positive association with spontaneous hatching. At the patient level, higher Δrel values of transferred embryos were associated with clinical pregnancy (OR 3.65, p = 0.009), whereas FF biomarkers and assisted hatching showed no significant association. Conclusions: Dynamic ZP thinning quantified by Δrel represents a promising indicator of embryo developmental competence. The concordance between embryo-level hatching behavior and patient-level clinical pregnancy suggests potential clinical relevance of ZP dynamics as an integrative embryological marker, warranting validation in larger cohorts. Full article

In the present study, vertebral bone tissues derived from Chongming crucian carp (Carassius carassius), a dominant species during the summer and autumn seasons on Chongming Island in the lower Yangtze River, were used to establish and characterize a Carassius carassius osteoblast cell line (COBC). The established COBCs were assessed using chromosome analysis, osteocalcin enzyme-linked immunosorbent assay (ELISA), and osteogenesis-related gene expression analysis. Additionally, cellular responses to environmental stress were assessed. The results showed that COBC exhibited optimal proliferation in L-15 medium supplemented with 20% fetal bovine serum at 28 °C. The histochemical staining assay results were all positive, thereby confirming that the isolated cells display typical osteoblast characteristics. Quantitative PCR analysis revealed that osteogenic marker genes, including runx2a and runx2b, were expressed at significantly higher levels in COBCs than in fish tissues. Under hypoxic stress, COBCs exhibited morphological changes, an increase in cell death, significant alterations in gene expression, and variations in antioxidant enzyme activity. These responses facilitate adaptation to hypoxic stress. This study established the first osteoblast cell line of the Chongming crucian carp and characterized its biological properties and response to hypoxic stress. These findings offer a valuable in vitro cell model and technical support for research on fish bone tissue biology and the assessment of environmental stress effects. Full article

A survey was carried out during 2023–2024, and 363 asymptomatic and symptomatic olive samples with deformed leaves, mosaic, and yellow spots were collected from different regions in Saudi Arabia. These samples were tested by ELISA against eight important olive viruses. To investigate the presence of these viruses in olive trees, PCR and RT-PCR techniques were employed using the virus-specific primers. The obtained results from serological tests indicated that 44.4% of the collected samples were found to be positive with at least one of the tested viruses. The most prevalent virus was OEGV (14.3%), followed by ArMV (11.9%), SLRSV (11.3%), CLRV (9.4%), TuYV (5%), TNV-D (4.4%), OMMV (3.6%), whereas OLV-1, OLV-2, CMV, TMV, OLV-3, OLYaV, and OLRSV were not positive in the tested samples. Single, as well as mixed infections, were observed in a number of samples with 9.4% and 34.7%, respectively. The nucleotide sequence analysis of PCR amplified fragments revealed 99.7–100% identity to OEGV, 95–99% to TuYV, 85–98% to OMMV, 83–93% to ArMV, 92–97% to CLRV, 84–98% to TNV-D, and 85–97% to SLRSV isolates, according to the pairwise nucleotide identity percentage calculated by SDT software. This is the first comprehensive survey to investigate the genetic diversity and phylogenetic relationship of seven olive viruses detected in olive trees in Saudi Arabia, which can provide the missing local epidemiological understanding. Full article

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with aortic pathologies such as atherosclerosis and thoracic aortic aneurysm posing significant risks due to their asymptomatic nature and potential fatal complications. This study investigates molecular mechanisms underlying CVDs by examining key cellular components of the aortic wall—vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages—and their responses to low-density lipoproteins (LDLs). Using in vitro models, we analyzed phenotypic characteristics, LDL internalization capacity, and secretion/expression of pro-inflammatory mediators (IL-6, IL-8, IL-1β, CCL2) in primary VSMCs (from tunica intima and media), fibroblasts (977hTERT), and THP-1 macrophages. Fluorescence staining with BDP 630/650 revealed that all cell types internalize LDLs, with macrophages showing the highest lipid accumulation. ELISA and RT-qPCR demonstrated cell-specific patterns of cytokine secretion and gene expression, both in control conditions and after LDL exposure. The results indicate that VSMCs and fibroblasts, normally involved in vascular tone maintenance and extracellular matrix (ECM) synthesis, acquire pro-inflammatory features under pathological conditions, including increased secretion of IL-6, IL-8, and CCL2. Macrophages exhibited enhanced expression of the scavenger receptor CD36 and pro-inflammatory cytokines (especially IL-1β) after LDL treatment. Full article

Preeclampsia involves an angiogenic imbalance, but circulating vascular endothelial growth factor A (VEGF A) remains inconsistently described, particularly in relation to maternal adiposity. We studied 90 second-trimester pregnancies, 30 uncomplicated and 60 with preeclampsia, recording maternal body mass index (BMI) and gestational age at sampling. Serum soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), and VEGF A were measured by enzyme-linked immunosorbent assay (ELISA), and the sFlt1-to-PlGF ratio was calculated. Preeclampsia was associated with higher pre-pregnancy and pregnancy BMI, lower PlGF, and an approximately threefold higher sFlt1-to-PlGF ratio, while sFlt1 alone was only borderline higher. VEGF A was elevated in preeclampsia and rose across higher sFlt1-to-PlGF ratio categories, supporting the interpretation of VEGF A within the integrated sFlt1,PlGF axis rather than as an isolated signal. Full article

Background/Objectives: The formation of a soft tissue seal through mucosal integration around dental implants is critical for potentially achieving long-term peri-implant health and clinical success. Understanding how different implant and abutment surfaces interact with individual layers of the oral mucosa remains limited. This study aimed to compare the differential attachment of tissue-engineered oral epithelium, connective tissue, and full-thickness human oral mucosa to various implant and abutment materials and surface topographies. Methods: Sand-blasted, large-grit, acid-etched (TiZr-SLA), machined TiZr (TiZr-M), machined zirconia (ZrO₂-M), polished zirconia (ZrO₂-P), and machined PEEK rods, along with commercially available titanium and ZrO₂ healing abutments, were inserted into 3D oral mucosal models following a 4-mm punch biopsy. Inflammation was induced using Escherichia coli lipopolysaccharide. Analyses included histology, PrestoBlue viability assay, scanning electron microscopy, and ELISA quantification of cytokines IL-1β, IL-6, and IL-8. Results: Epithelial attachment was greater on TiZr-SLA, ZrO₂-P, and PEEK-M (p < 0.05 and p < 0.01) surfaces compared with TiZr-M and ZrO₂-M. TiZr-SLA exhibited the highest connective tissue attachment (p < 0.05). Commercial titanium and ZrO₂ healing abutments demonstrated the highest post-pull PrestoBlue viability and overall soft tissue attachment. SEM confirmed cell retention on all implant surfaces. Elevated IL-1β levels were detected in models exposed to ZrO₂-M and PEEK-M, whereas IL-6 and IL-8 levels were not influenced by any material or surface topography. Conclusions: In vitro epithelial and connective tissue responses are influenced by implant material, surface topography, and design. Rough TiZr-SLA surfaces promote superior connective tissue attachment, while smooth commercial abutments support optimal overall soft tissue integration. These findings highlight the importance of surface engineering in preclinical optimization of peri-implant soft tissue attachment. Full article

Objectives: This study aimed to evaluate the effectiveness and safety of paracetamol 1000 mg/ibuprofen 300 mg administered three times daily (TID) in comparison with ibuprofen 600 mg TID in the management of patients with acute moderate/severe non-specific low back pain (LBP). Methods: This was a phase IV, randomized, open-label, parallel-group study conducted in adults with moderate/severe LBP (Visual Analogue Scale [VAS] score ≥ 40 mm). Results: A total of 171 patients were included in the modified intention-to-treat (m-ITT) population (paracetamol 1000 mg/ibuprofen 300 mg: 83 patients; ibuprofen 600 mg: 88 patients). No significant between-group difference on the primary endpoint (SPID 0–3 days) was found. Patients were mainly women (60.2% and 55.7%), with a mean age of 42.8 and 43.3 years, respectively. In the m-ITT population, the effectiveness, safety and tolerability were similar between groups. In the per-protocol population, clinical pain reduction was observed with paracetamol 1000 mg/ibuprofen 300 mg. At visit 1, significant differences in the Clinical Global Impression–Improvement scale (paracetamol 1000 mg/ibuprofen 300 mg: 63.9%; ibuprofen 600 mg: 45.5%; p = 0.0137) and a trend favouring paracetamol 1000 mg/ibuprofen 300 mg in Patients’ Global Impression of Change (63.9% vs 44.4%; p = 0.0539) score were observed. Conclusions: Given the open-label design and the exploratory nature of study’s secondary endpoints, no claims of superiority can be drawn; but our findings confirm that good management of acute moderate/severe LBP can be achieved with multimodal therapy with paracetamol 1000 mg/ibuprofen 300 mg. EudraCT Number: 2020-005278-86 (EudraCT Number 2020-005278-86—Clinical trial results—EU Clinical Trials Register; date of registration: 14 June 2021). Full article

The aim of this work is to prepare and characterize a composite adsorbent comprising the hydrophilic ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM-Ac] composite supported on mesoporous silica gel for application in adsorption heat storage systems. Water adsorption/desorption isotherms were measured gravimetrically at T = 40, 50, 70 °C across a relative humidity (RH) range of 0–0.8, demonstrating a high adsorption capacity (up to 0.71 g/g at 50 °C and RH = 0.8, for a 50 wt % [EMIM-Ac] loading). Full process reversibility and negligible ad/desorption hysteresis were also verified. Thermal stability of the prepared silica/[EMIM-Ac] composites was confirmed up to approximately T = 200 °C. Structural stability of samples subjected to repeated ad/desorption aging cycles was verified via FT-IR, High-Resolution Solid-State NMR, and Time-Domain NMR spectroscopy. Finally, the thermodynamic analysis based on adsorption experimental data indicated that the silica/[EMIM-Ac] composite is highly suitable for adsorption heat storage, providing a volumetric density of 600–920 MJ/m³ at regeneration temperatures below 100 °C. Full article

Endothelial cells are key regulators of vascular homeostasis, and their dysfunction plays a central role in the development of atherosclerosis and other cardiovascular diseases. Multinucleated variant endothelial cells (MVECs) have been described in pathological vascular regions; however, their functional properties remain poorly characterized. The aim of the present study was to compare lipid handling, inflammatory activation, barrier-associated features, and secretory profiles of typical endothelial cells (TECs, EA.hy926 line) and MVECs under low-density lipoprotein (LDL) exposure. MVECs were generated by polyethylene glycol-induced fusion of EA.hy926 cells and incubated with LDL under standardized conditions. Intracellular cholesterol accumulation was assessed biochemically, cytokine secretion was quantified by ELISA, gene expression of inflammatory, endothelial, junctional, and vasoactive markers was analyzed by quantitative real-time PCR, and the endothelial secretome was characterized using data-independent acquisition liquid chromatography–tandem mass spectrometry (DIA-LC-MS). MVECs demonstrated enhanced cholesterol accumulation compared with TECs following LDL exposure. At the transcriptional level, MVECs were characterized by elevated basal expression of proinflammatory markers, including IL1B, IL6, and NFKB1, and showed a markedly amplified IL6 and IL8 response to LDL. In parallel, MVECs exhibited reduced expression of genes associated with antioxidant defense (SOD1), barrier integrity (TJP1), and hemostatic function (VWF). Consistent with transcriptional data, mass spectrometry-based secretome analysis revealed decreased secretion of von Willebrand factor (vWF), vascular endothelial growth factor C (VEGFC), and endothelin-1 (EDN1) by MVECs, accompanied by increased secretion of tissue-type plasminogen activator (t-PA). Functional enrichment analysis of secretome-associated proteins highlighted pathways related to extracellular matrix–receptor interaction, focal adhesion, cell adhesion molecules, complement and coagulation cascades, and leukocyte transendothelial migration. In contrast, TECs demonstrated a more pronounced transcriptional response in EDN1, consistent with their role in vascular tone regulation. Immunocytochemical analysis further revealed altered subcellular distribution of the tight junction protein ZO-1 in MVECs, indicating junctional destabilization. Taken together, these results indicate that MVECs represent a distinct endothelial phenotype characterized by enhanced lipid accumulation, sustained proinflammatory activation, altered secretory signaling, and reduced barrier and hemostatic potential. Such features suggest that MVECs may contribute to the maintenance of chronic endothelial dysfunction and vascular inflammation under conditions of lipid overload. Full article

Background/Objectives: Astrocytes play a critical role in maintaining brain homeostasis and are increasingly recognized as active contributors to neurodegenerative processes. Metabolic dysfunction in astrocytes has been implicated in the onset and progression of Alzheimer’s disease (AD), yet the underlying metabolic alterations remain poorly characterized. Methods: We used an optimized protocol for untargeted metabolomic profiling of both intracellular and extracellular compartments of primary human astrocytes derived from AD patients and healthy subjects (HS) using ¹H nuclear magnetic resonance (NMR) spectroscopy. Cells were treated with oligomeric Aβ_1-42 to model pathological conditions. Results: Aβ_1-42 treatment induced intracellular metabolic alterations in both AD and HS astrocytes, including a consistent reduction in phosphocreatine, potentially indicating impaired energy-buffering capacity. Notably, a decrease in β-alanine was observed only in AD astrocytes, suggesting alterations in carnosine-related antioxidant defence. Analysis of conditioned media revealed differential responses between groups: AD astrocytes showed increased extracellular levels of 2-oxoglutarate, citrate, and glycine, whereas HS astrocytes exhibited reduced extracellular levels of leucine and isoleucine, suggesting distinct adaptive metabolic responses to Aβ-induced stress. However, none of these differences remained statistically significant after correction for multiple testing. Conclusions: These findings suggest that NMR-based metabolomics can detect subtle metabolic shifts in human astrocyte models of AD and HS exposed to amiloidogenic challenge. Given the limited sample size and the exploratory design adopted, the results should be interpreted as preliminary and require validation in larger, better-matched cohorts. Nevertheless, this study provides a methodological framework and generates biologically plausible hypotheses regarding astrocyte metabolic responses relevant to AD pathophysiology. Full article

This study evaluated the effects of the dietary administration of a glycosylated form of active vitamin D (calcitriol, 1,25(OH)₂D₃) combined with ursolic acid (UA) and oleanolic acid (OA) triterpenes on sow health and productivity. Twenty-four third-parity Landrace × Large White sows were allocated at day 108 of gestation into three groups: a control group receiving 1800 IU/kg of vitamin D₃, and two treatment groups receiving the control diet supplemented with either 0.64 µg/kg (ACTD1) or 0.96 µg/kg (ACTD2) of glycosylated 1,25(OH)₂D₃ plus 140 or 210 µg/kg of UA + OA (4:1 ratio), respectively. Diets were administered from late gestation through the end of lactation. Farrowing duration, sow body weight, backfat thickness, and litter growth were recorded. Blood samples collected at key physiological stages were analyzed for pro-inflammatory cytokines, mineral homeostasis, endocrine markers, and serum proteome. Farrowing time was reduced in both treatment groups compared with the control (p < 0.05). Treated sows exhibited lower backfat thickness at the end of lactation and improved litter weights at farrowing, after cross-fostering, and at weaning (p < 0.05). Plasma pro-inflammatory cytokines (TNF-α, IL-1α, and IL-1β) were reduced at the end of lactation in ACTD1 and ACTD2 sows, with TNF-α and IL-1β already decreased after farrowing (p < 0.05). Treated sows also displayed decreased plasma parathormone concentrations at the end of lactation, along with increased circulating 1,25(OH)₂D₃ and calcium concentrations after farrowing and at lactation end (p < 0.05), while plasma phosphate levels remained unchanged. Proteomic analysis supported the systemic availability of the supplemented compounds and their involvement in metabolic and inflammatory pathways rather than calcium transport or vitamin D binding mechanisms. Overall, this nutritional strategy influenced the immune modulation while maintaining mineral homeostasis via modest endocrine adaptations. Larger-scale trials are warranted to confirm these results and to evaluate their practical applicability under commercial production conditions. Full article

Objectives: Dendrobine (DDB) is one of the active ingredients in Dendrobium and has been reported to have significant neuroprotective properties. Nevertheless, the precise mechanisms underlying its action have not been fully clarified. The microglial imbalance of polarization is regarded as one of the key determinants in the etiology of neurodegenerative conditions, in the contribution of neuroinflammation. The recovery of M1/M2 balance and the inhibition of over-production of the pro-inflammatory effects have become major topics in modern studies of preventing and treating neurodegenerative diseases. Methods: Therefore, the present study aimed to explore the effects of DDB on the Lipopolysaccharide (LPS)-induced neuroinflammatory model in BV2 microglial cells and the potential molecular mechanisms of microglial M1/M2 polarization. Result: The results showed that DDB significantly suppressed Nitric Oxide (NO) release and ROS levels in LPS-induced BV2 cells. ELISA, qPCR, Western blot, and immunofluorescence results indicated that DDB reduced pro-inflammatory mediators Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and nterleukin-1 beta (IL-1β) and increased anti-inflammatory mediators Interleukin-10 (IL-10) and Arginase-1 (Arg-1). Consistently, it decreased M1-like markers Inducible Nitric Oxide Synthase (iNOS) and Cluster of Differentiation 16/32 (CD16/32) while increasing M2-like/repair-associated markers (CD206 and Arg-1), suggesting a shift toward a more anti-inflammatory microglial activation profile based on the assessed marker pane. Conclusions: These results suggested that DDB can suppress the production of inflammatory cytokines and modulate microglial polarization, which indicated that DDB can be used as an effective compound in the prevention of neuroinflammation-related disorders. Full article

Treponema pallidum is the etiological cause of syphilis, and in recent years, reemergence has been reported, especially among men who have sex with men and people living with HIV (PLWH). Certain cytokines may act as hallmark biomarkers in the progression of syphilis in PLWH, and studying how the immune system works against T. pallidum is important, especially in PLWH, whose immune system is compromised. We evaluated the serum expressions of IFN, TNF, IL-10, TGF-β1 and IL-17 in men living with HIV (MLWH) and their association with distinct stages of syphilis. We recruited MLWH from March to October 2022. A blood sample was requested, syphilis was detected using the reverse algorithm, and antibodies were titrated to determine the stage. Each of the cytokines studied was quantified using commercial ELISA kits. The following groups were formed: active syphilis (n = 217), cured syphilis (n = 134), and without syphilis (n = 159). The prevalence of elevated TGF-β1 differed between groups, being highest in individuals with active syphilis (51.6%; median 319 pg/mL), followed by those with cured syphilis (41.0%; median 137.0 pg/mL). Younger participants and persons without a history of sexually transmitted infections were more likely to present with high TGF-β1 levels. TGF-β1 may act as a biomarker in active syphilis and could suppress the inflammatory response against spirochetes. Full article