Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

Unraveling complex mechanisms of telomere biology is central to understanding the close link between aging and inflammation. Telomeres are repetitive heterochromatin DNA structures at the ends of eukaryotic chromosomes, and their length is universally accepted as a marker of biological aging. Telomeres progressively shorten with every cell division until they ultimately trigger cellular senescence and apoptosis. Telomere shortening is also promoted by chronic inflammation and oxidative stress. Chronic inflammation and oxidative stress have been shown to be key drivers of age-related diseases, including neurodegeneration, cardiovascular disease, and cancer. Telomerase is central regulator at the intersection of genomic stability, mitochondrial function, epigenetic integrity, and proteostasis. Through its direct and indirect actions, telomerase modulates inflammatory pathways that drive aging and age-related diseases, highlighting its potential as a therapeutic target to mitigate inflammaging and extend healthspan.

Purpose: This study aimed to evaluate the therapeutic efficacy of EB-203 using a zebrafish model that exhibits diabetic retinopathy like vascular alterations.

Methods: To assess the toxicity of EB-203, embryos obtained from Tg(flk:EGFP) adult zebrafish were exposed to various concentrations of the compound (6.25, 12.5, 25, 50, 100, 200, and 400 μg/mL). To evaluate its efficacy against DR-like phenotypes, normally developed embryos at 3 days post-fertilization (dpf) were treated with EB-203 under hyperglycemic conditions. At 6 dpf, retinal tissues were isolated to measure retinal vessel diameter changes. Microarray analysis was performed to identify changes in DR-related gene expression following EB-203 treatment, and selected markers were validated using RT-PCR. Histological alterations in the retinal layers were analyzed through H&E staining, TUNEL assays, and immunofluorescence.

Results: In the zebrafish model, EB-203 administration ameliorated retinal vessel dilation like phenotypes and improved vascular permeability like alterations. Moreover, EB-203 reduced expression of inflammatory markers in the retina by downregulating the NF-κB signaling pathway, thereby alleviating NPDR like features in hyperglycemic larvae.

Conclusions: EB-203 was found to reduce microvascular leakage changes, edema features, and inflammatory responses associated with NPDR-like phenotypes, suggesting its potential to limit progression toward PDR conditions. Overall, EB-203 demonstrated significant efficacy in improving NPDR like retinal pathology in zebrafish and holds promise as a potential therapeutic candidate for DR.

In this study, we present an ultrafast, efficient, and broadly applicable strategy for cell membrane modification via tyrosine-selective bioconjugation using diazonium salt derivatives. This chemical approach enables both one-step and two-step functionalization of adherent, suspension, and primary cells with a wide range of ligands, including imaging probes, carbohydrates, biotin, and proteins, without inducing cytotoxicity or immune activation. Cell membrane engineering through bioconjugation has emerged as a powerful tool in biomedical research, given the central role of the membrane in signaling, transport, and cell-cell interactions. In contrast to conventional glyco-engineering methods, which typically require multiday incubations and can induce cellular stress, our approach achieves rapid, precise, and high-density surface functionalization in less than one hour, with improved reproducibility and biological compatibility. We further demonstrate the applicability of this strategy across diverse cell types, including immortalized cell lines and clinically relevant primary cells such as peripheral blood mononuclear cells (PBMCs) and human natural killer (NK) cells. Notably, surface grafting of an EGFR-targeting Nanofitin enhances the cytotoxic activity of NK cells against EGFR-positive cancer cells. In addition, we show that the bioconjugated signal progressively diminishes over successive cell divisions, providing a self-limiting and transient alternative to permanent genetic modifications such as CAR-based engineering, thereby potentially reducing the risk of prolonged immune activation. Finally, the ability to store pre-functionalized cells at -80 °C increases the practicality of this platform for future ready-to-use applications. Overall, this versatile and non-genetic bioconjugation strategy offers a compelling alternative to existing technologies for applications in targeted therapy, diagnostics, and cell-based immunotherapy.

Introduction: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.

Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to September 2025 identified randomized controlled trials (RCTs) and observational studies comparing at least two anti-VEGF agents in nAMD. Eligible studies reported outcomes of best-corrected visual acuity (BCVA) change, visual gain ≥ 15 letters, mortality, or arteriothrombotic events. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. A frequentist network meta-analysis estimated mean differences (MD) and odds ratios (OR) with 95 % confidence interval (CI). The protocol was registered in PROSPERO (CRD42025631298).

Results: Sixteen studies involving 6758 participants (follow-up 3-24 months) met the inclusion criteria. For BCVA improvement, Aflibercept had the highest surface under the cumulative ranking curve (SUCRA) ranking (0.80), although all agents showed similar mean differences that were not statistically significant: aflibercept (MD 0.80; 95 % CI -1.20-2.80), Ranibizumab (0.64; -1.87-3.15), Bevacizumab (0.60; -2.02-3.22), Faricimab (2.20; -0.69-5.09), and Brolucizumab (4.20; -5.97-14.36). The larger point estimate for Brolucizumab reflects imprecision rather than superior visual efficacy. Mortality was lowest with Aflibercept (risk ratio (RR) 0.76; 95% CI 0.41-1.55). For arteriothrombotic events, no statistically significant differences were observed between anti-VEGF agents. Comparisons between Aflibercept and Bevacizumab (RR 1.11; 95% CI 0.60-2.07), aflibercept and Ranibizumab (RR 0.77; 95% CI 0.49-1.21), and Bevacizumab and Ranibizumab (RR 0.88; 95% CI 0.60-1.30) showed wide confidence intervals, reflecting substantial imprecision. Certainty of evidence (GRADE) ranged from moderate to low.

Conclusion: All anti-VEGF agents stabilize or improve vision in nAMD. Aflibercept may provide the most favorable efficacy-safety balance, Faricimab offers promising durability, and Brolucizumab demonstrates large visual gains with potential safety concerns. Further head-to-head and long-term real-world studies are needed to optimize individualized treatment strategies.

Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as long COVID, encompasses a constellation of persistent symptoms lasting for at least three months after acute SARS-CoV-2 infection and not explained by alternative diagnoses. The multifactorial pathophysiology underlying PASC remains incompletely understood, limiting the development of effective management strategies. Increasing evidence suggests that both immune dysregulation and hemostatic imbalance play central roles in post-COVID-19 complications. Megakaryocytes, key regulators of platelet production and coagulation, have emerged as potential contributors to sustained thrombo-inflammatory processes following SARS-CoV-2 infection. In parallel, afucosylated IgG antibodies have been strongly implicated in exaggerated immune activation and hyperinflammatory responses during acute COVID-19. The persistence of such antibody glycosylation patterns beyond the acute phase raises the possibility that they may also contribute to chronic immune and vascular alterations observed in PASC. This narrative review explores the potential interplay between megakaryocyte dysfunction and afucosylated IgG antibodies in the pathogenesis of PASC. By examining mechanisms identified during acute SARS-CoV-2 infection, we discuss how prolonged immune-hemostatic crosstalk may promote persistent inflammation, endothelial dysfunction, and microvascular abnormalities. Understanding these interconnected pathways may provide mechanistic insight into the heterogeneity of PASC manifestations and help identify novel therapeutic targets for long-term post-COVID-19 sequelae.

Background: and Aim: Natural substances have always been used to treat various diseases and cancers. Cinnamaldehyde has been previously reported to have antioxidant, antidiabetic and anticancer potential. This study aims to investigate the effect of caffeic acid and cinnamic acid compared to cinnamic aldehyde on the viability of MCF-7 and MDA-MB-231 cell lines in correlation with the effect on the non-cancerous cell line: HB-2.

Materials and methods: Cell viability assays were conducted using the MCF-7 and MDA-MB-231 breast cancer cell lines in correlation with the HB2 cell line. The migration assay has been done using all three cell lines using the scratch assay. Molecular docking was achived using SwissDock SwissDrugDesign of method AutoDock Vina 1.2.0 docking parameters of the full protein binding ligand samling exhaustivity of 4 (Molecular Modeling Group, University of Lausane and Swiss Insisute of Bioinformatics. Schematics was created using BioRender © 2024. Images of proteins and ligands were rendered using BIOVIA, BIOVIA, Dassault Systèmes, Discovery Studio Visualizer, v17.2, San Diego: Dassault Systèmes, 2016. The PTP inhibitory effect was calculated using PNPP as the substrate, with compounds serving as inhibitors in correlation with the non-inhibited control.

Results: Both Caffeic acid and cinnamic acid had an inhibitory effect on the cell viability of the MDA-MB-231 cell line. MCF-7 studies showed that caffeic acid had an inhibitory effect on cells, but cinnamic acid had this effect only on MCF-7 cells. HB2 cells have shown reduced viability, which is significantly higher than that of MCF-7 cell lines.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory dysfunction, with prominent roles in cholinergic deficits and synaptic plasticity impairments. Vitisin B, a resveratrol tetramer derived from Vitis vinifera, exhibits potent antioxidant and neuroprotective properties. However, its potential to influence cognitive function in AD models remains inadequately explored. In this study, we first tested vitisin B in an in vitro model using SH-SY5Y cells exposed to scopolamine-induced cytotoxicity, where vitisin B significantly enhanced cell viability and promoted cell survival. We evaluated its therapeutic potential in vivo using both systemic administration and direct delivery into the third ventricle of the brain in a scopolamine-induced AD mouse model. Across both administration routes, vitisin B exerted a broad pro-cognitive effect, restoring multiple domains of learning and memory disrupted by scopolamine. Vitisin B recovered spatial working memory in the Y-maze, normalized exploratory activity in the open field, improved recognition memory in the novel object recognition (NOR) test, and enhanced long-term memory retention in the passive avoidance assay. This treatment restored cognitive function, alleviated cholinergic deficits, increased hippocampal brain-derived neurotrophic factor (BDNF) levels, and enhanced synaptic plasticity. These results suggest that vitisin B exerts reliable cognitive and neuroprotective effects through both systemic and cerebral administration, highlighting its potential as a promising therapeutic compound for restoring cholinergic function and enhancing hippocampal synaptic plasticity in AD.