Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

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.

Oxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Cannabis sativa L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant's antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from Cannabis sativa L. in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100 µM). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed in silico. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-κB2, IL-6, and IL-8. In silico docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that Cannabis sativa L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage.

5-Fluorouracil (5-FU) is a first-line chemotherapeutic for colorectal cancer (CRC), yet its clinical application is limited by low bioavailability, rapid systemic clearance, and off-target toxicity. We developed tunable PEGylated bovine serum albumin (BSA) nanoparticles as a nanocarrier platform for 5-FU delivery, aiming to improve drug encapsulation, enhance cytotoxic selectivity toward CRC cells, and modulate oxidative and immune-related responses. Using PEG of varying molecular weights (2, 4, and 10 kDa), monodisperse nanoparticles (71-111 nm) were synthesized via a desolvation method and characterized by multi-angle dynamic light scattering, transmission electron microscopy, microscale thermophoresis and HPLC. PEGylation improved colloidal stability and increased 5-FU loading efficiency, particularly at higher drug input concentrations. Binding studies revealed molecular weight- and concentration-dependent interactions of PEG and 5-FU with albumin, influencing nanoparticle architecture and physicochemical properties. Biological evaluation was performed across CRC cell lines (HT-29, Caco-2), non-cancerous fibroblasts (L929), and THP-1-derived macrophages. PEGylated BSA-FU nanoparticles exhibited selective, long-term cytotoxicity toward colorectal cancer cells. In macrophages, PEGylated formulations modulated phagocytic activity and oxidative stress responses in a formulation-dependent manner, indicating that PEGylation alters-rather than uniformly suppresses-immune cell interactions. These findings highlight the importance of rational PEG architecture optimization and provide a strong foundation for future in vivo studies addressing repeated dosing, immune interactions, and translational potential in colorectal cancer therapy.

Osteoporosis is a chronic disorder marked by bone wasting and increased bone fragility. Targeted inhibition of osteoclastogensis is currently the core therapeutic strategy. Hexahydrocurcumin (HHC), derived from Zingiberis Rhizoma, has been shown to exhibit anti-inflammatory and antioxidant properties; however, its effects on osteoclasts regulation and osteoporosis pathogenesis remain unexplored. We conducted this study to observe the influence of HHC on RANKL-mediated osteoclast precursor differentiation and OVX-dependent osteoporotic mice. In this study, we revealed that HHC significantly attenuated the generation and bone resorptive function of osteoclasts induced by RANKL in vitro, which was achieved by targeting and inhibiting the phosphorylation of c-Src, a critical molecule in osteoclast differentiation. Next, HHC inhibited the subsequent Ca²⁺ influx and NFATc1 nuclear translocation, thereby suppressing the expression of osteoclastogenic regulators such as Acp5 and Mmp9. Furthermore, we validated that HHC inhibits osteoclastogenesis by targeting c-Src through siRNA-mediated silencing of c-Src. In the in vivo study, HHC notably alleviated bone loss in OVX-dependent osteoporotic mice. These findings suggest that HHC alleviates osteoporosis by inhibiting osteoclastogenesis via targeting c-Src, which provide preliminary evidence for the potential of HHC for the treatment of osteoporosis.