Search Results (1,617)

Complement and pathogenic antibodies act independently and together to mediate the pathology of many autoimmune diseases. To address these drivers of disease, we generated a monoclonal antibody (mAb), CSL305, that binds and inhibits both complement and the neonatal Fc (fragment crystallizable) receptor FcRn. The fragment antigen binding (Fab) portion of CSL305 was engineered to bind both human C2 (huC2) zymogen and the active fragment huC2b to inhibit the classical and lectin complement pathways in vitro, and C3b deposition on primary lung endothelial cells using a 3-dimensional microvascular model system. Engineering of a triple amino acid mutation (“YPY” motif) into the Fc region of CSL305 increased its affinity to FcRn at both acidic and neutral pH, allowing it to also act as a potent FcRn antagonist. Intracellular trafficking experiments demonstrated that CSL305, but not the wild-type (WT) mAb lacking the YPY motif, was able to block immunoglobulin G (IgG) recycling in vitro. The generation of a high resolution 2.6Å crystal structure of CSL305 Fab region bound to huC2b showed that the epitope lies directly over the huC2b catalytic triad, providing evidence of its complement mechanism of action as a neutralising mAb. Early pharmacokinetic (PK)/pharmacodynamic (PD) studies using CSL305 in cynomolgus monkeys demonstrated both complement inhibition and FcRn antagonism in vivo, with reductions in complement classical pathway activity and endogenous IgG observed following single intravenous (IV) administration. CSL305 thus represents a dual-functional mAb as a potential therapeutic candidate. Full article

Edible mushrooms have long been valued as functional foods and traditional remedies, yet a significant developmental gap hinders their transition from nutraceuticals to standardized pharmaceutical ingredients. This narrative review provides a comprehensive and integrative analysis of edible mushroom-derived bioactive compounds as emerging candidates for pharmaceutical development. It examines major chemical classes, including polysaccharides (e.g., β-glucans), proteins (e.g., lectins, FIPs), triterpenoids (e.g., ganoderic acids), nucleosides (e.g., adenosine and cordycepin), and phenolic compounds, which underpin immunomodulatory, anticancer, antioxidant, anti-inflammatory, and metabolic activities. Beyond bioactivity, the review critically examines the downstream processing pipeline required for translation into pharmaceutical ingredients, encompassing controlled biomass production, pre-extraction processing, extraction technologies, isolation and purification strategies, and structural elucidation techniques. Key bottlenecks are identified, including bioavailability limitations of β-glucans (2–5%), lack of standardization, limited human clinical evidence, and regulatory constraints, explaining why robust preclinical evidence has not consistently translated into clinical success. Emerging solutions are also highlighted, including application of multi-omics tools, nano-encapsulation strategies, and synthetic biology approaches to improve scalability and reproducibility. By synthesizing research on natural product chemistry, biotechnology, and pharmacology, this study maps the journey of edible mushrooms from traditional dietary components to pharmaceutical-grade ingredients, providing a focused resource for researchers and industry stakeholders aiming to navigate mushroom-based drug development. Full article

Chickpea (Cicer arietinum L.) generally contains lower levels of these compounds than many other legumes, yet information on Hungarian chickpea cultivars is scarce. This study aimed to characterize protein-based antinutritional factors in twenty chickpeas grown under different agroclimatic conditions over three consecutive years (15 samples from seven Hungarian cultivars from three cultivation areas, and five commercially available foreign genotypes). Protein profiles were examined by SDS-PAGE and native PAGE, while trypsin inhibitor activity (TIA) was quantified spectrophotometrically according to ISO 14902, and lectin activity was determined using a hemagglutination assay. SDS-PAGE revealed highly similar protein patterns among samples, indicating comparable overall protein composition. Native PAGE combined with activity staining confirmed the presence of Kunitz-type trypsin inhibitors, with multiple isoforms detected, but no Bowman–Birk-type inhibitor activity was observed. TIA values were low (0.49–4.07 mg inhibited trypsin/g), and lectin activities were generally low (1–2.5 HU/mg flour; only one sample reached 5 HU/mg) or undetectable. Neither cultivation area nor growing year had a significant effect on TIA or lectin activity, confirmed by statistical analyses. Overall, Hungarian chickpea varieties exhibited low and stable levels of antinutritional proteins, supporting their favorable nutritional quality and suitability for human consumption and expanded cultivation under Hungarian agroclimatic conditions. Full article

Background: Oral squamous cell carcinoma (OSCC) remains clinically challenging, particularly in advanced disease, where treatment resistance limits therapeutic outcomes. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a potential anticancer vulnerability. Galectin-1 (Gal-1/LGALS1), a β-galactoside–binding lectin frequently overexpressed in OSCC, is associated with tumor progression and unfavorable prognosis; however, its involvement in ferroptosis regulation remains incompletely understood. Methods: To investigate whether Triptolide (TPL) influences ferroptosis-associated responses through Gal-1 modulation, OSCC cell lines (SAS and HSC-3) were treated with TPL and analyzed for cell viability, lipid reactive oxygen species (ROS) accumulation, and glutathione peroxidase 4 (GPX4) expression. Publicly available The Cancer Genome Atlas (TCGA) datasets were examined to evaluate Gal-1 expression patterns and survival associations. An OSCC xenograft mouse model was further used to assess the antitumor effects of TPL and changes in ferroptosis-related markers in vivo. Results: TPL treatment reduced cell viability and increased lipid ROS accumulation in OSCC cells, accompanied by downregulation of GPX4 expression. Gal-1 expression was also decreased following TPL exposure in vitro and in xenograft tumors. Analysis of TCGA data revealed that elevated Gal-1 expression was significantly associated with poorer overall survival in OSCC patients. Conclusions: These findings indicate that TPL induces ferroptosis-associated responses in OSCC and suggest that this effect is partly mediated through modulation of Gal-1 expression. Gal-1 may represent a clinically relevant factor influencing ferroptosis susceptibility, and targeting this pathway warrants further investigation as a potential therapeutic strategy for OSCC. Full article

Recognition and binding to β-galactose-containing carbohydrates and lipids are crucial for several fundamental biological processes that are mediated primarily by a family of proteins known as galectins (S-type lectins). Galectins in the human placenta regulate critical processes such as maternal–fetal immune tolerance, trophoblast invasion, vascular remodeling and angiogenesis, ensuring proper fetal development and preventing pregnancy complications such as preeclampsia and miscarriage. Gestational diabetes mellitus (GDM) is a widespread complication of pregnancy, affecting approximately 1 in 7 pregnancies, and its incidence is increasing globally, indicating a particularly strong association with the obesity pandemic. Profiles of placental expression and distribution of individual galectins significantly change during the course of GDM. This is accompanied by placental dysfunction, which is especially severe with poor glycemic control. The aim of this review is to present the current state of knowledge on the involvement of abnormal galectin signaling in the pathomechanisms of GDM-associated placental dysfunction. Further research is needed to determine whether changes in placental galectins occur secondary to metabolic abnormalities in GDM or are involved as a primary cause. Galectins present in placental tissue and serum should be validated as potential biomarkers of GDM. Full article

Lectins are carbohydrate-binding proteins that specifically bind to sugar groups associated with other molecules. Several studies have reported that these proteins can also modulate the activity of antibiotics against multidrug-resistant (MDR) strains in addition to interacting with carbohydrates. This study reports that gentamicin exhibits enhanced antibacterial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacterial strains when complexed with Crenomytilus grayanus lectin (CGL). Enzyme-linked lectin, thermofluor, and isothermal titration calorimetry assays revealed that gentamicin interacts with CGL through a domain distinct from the carbohydrate recognition domain. An increase in antibacterial activity was observed when lectin and antibiotic were used together against S. aureus in living systems—specifically, sea urchin (Strongylocentrotus nudus) embryos. Full article

Background/Objective: Long COVID is an important cause of disability following SARS-CoV-2 infection; yet, its underlying mechanisms are not completely understood. One proposed mechanism is the long-lasting dysregulation of the immune complement system. This systematic review is the first to summarize the current evidence and evaluate the potential role of long-lasting complement activation in people with long COVID. Methods: A systematic electronic search on PubMed, MEDLINE, CINAHL, and Embase was conducted up to 15 October 2025, to identify studies investigating complement activation in people with the post-COVID-19 condition. The Newcastle–Ottawa Scale was used to evaluate the risk of bias and methodological quality. Results: Among the 247 studies initially identified, eleven met the inclusion criteria, comprising 1435 individuals (age: 48.5 years, 70% females) with long COVID and 1124 controls (age: 43.6 years, 60% females). All studies were of a high quality, with scores ranging from 7 to 8 stars (mean: 7.6 ± 0.5). The activation of the classical complement pathway was investigated in nine studies, whereas the lectin, alternative, and terminal complement pathways were each assessed in three studies. Multiple studies investigated several complement pathways. The results were heterogeneous since several markers of complement activation spanning the classical (C2, C4a, C4b, and C1s-C1INH), alternative (Ba, iC3b, and Factor D), and terminal (C5bC6, C5a, C9, and TCC) pathways were elevated, whereas other markers were not significantly different (C3, C4, and C4d) between patients with/without long COVID. In addition, markers spanning the lectin complement pathway (MBL, and MASP1-C1INH) were not significantly different between individuals with and without long COVID. Conclusions: The current evidence suggests potential long-lasting complement system dysregulation in individuals with long COVID, although the clinical significance remains controversial, due to heterogenous findings. Specific post-COVID symptom clusters, such as fatigue, dyspnea, or brain fog, have been linked to a distinct pattern of complement dysregulation. Substantial methodological heterogeneity, including differences in follow-up periods, complement markers, assessment methods, and control groups, along with the small number of available studies, underscores the need for further research to clarify the mechanisms linking complement dysregulation to long COVID. Full article

Glycosylation depends on luminal nucleotide sugars delivered by solute carrier 35 (SLC35) transporters. SLC35A3 is a uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter. In humans, biallelic mutations in SLC35A3 cause arthrogryposis, mental retardation, and seizures (AMRS). To define how loss of SLC35A3 function reshapes the neural glycome, we profiled N-, O-, and glycosaminoglycans (GAGs) in Slc35a3 knockout mouse brains. N- and O-glycans were analyzed by MALDI-TOF MS, and GAG disaccharides were quantified by anion-exchange HPLC. Knockout mouse brains exhibited attenuation of complex-type N-glycans with a reciprocal rise in high-mannose species, as revealed by MALDI-TOF MS profiling. In contrast, ConA lectin blotting showed no significant change, consistent with its preferential detection of mannose-rich glycans. Branching analysis revealed loss of tri- and tetra-antennary structures compared with biantennary species. O-glycan profiling showed core-2-type species (Hex₂HexNAc₂ backbone) decreased. The dominant disialyl core-1 remained stable. Total GAG output (chondroitin/dermatan sulfate, heparan sulfate, and hyaluronan) was preserved. These findings support a microdomain model in which SLC35A3 acts as a locally effective supplier of UDP-GlcNAc to MGAT4 (branching N-acetylglucosaminyltransferase that installs the β1,4-GlcNAc arm) in the brain, while alternative routes buffer UDP-GlcNAc delivery for GAG and mucin-type O-glycan biosynthesis. Accordingly, AMRS may be attributed to impaired higher-order N-glycan branching in the brain. Full article

Marine ecosystems have yielded a remarkable diversity of bioactive metabolites with relevance for antiviral drug discovery. This article reviews recent advances in marine-derived compounds investigated as anti-HIV agents. Metabolites, such as sulfated polysaccharides, lectins, alkaloids, and terpenoids, display inhibitory activity across multiple stages of the HIV life cycle, including viral entry, reverse transcription, integration, and maturation. From sponge-inspired development of AZT to the application of Griffithin in clinical trials for the prophylaxis of the HIV infection, recent discoveries showcase the chemical diversity of marine ecosystems and validate their utility as hit and compound sources in drug discovery. We highlight possible mechanisms of action, as well as translational hurdles from research to clinical trials. Overall, marine biodiversity represents a valuable and underexploited reservoir for the development of novel HIV therapeutics. Full article

Glycan-mediated processes can be critical determinants of viral attachment and entry, yet for enveloped RNA viruses, including SARS-CoV-2, their mechanistic roles remain incompletely defined. This review synthesizes current structural and functional evidence for glycan engagement during SARS-CoV-2 attachment and entry. We describe the general viral entry pathways and their reliance on glycan recognition, followed by the interactions of the SARS-CoV-2 spike glycoprotein with host glycans, including ABO(H) blood group antigens, sialylated glycans, and endogenous lectins. Based on structural biology, glycobiology, and virology, we focus on how the spike protein exploits both glycan motifs and lectin receptors to enhance attachment, promote cellular uptake, or modulate host tropism. We contextualize these mechanisms by comparing glycan dependencies across other human viruses, including the influenza virus, HIV, and norovirus. Finally, we provide a comparative virological perspective to derive broad evolutionary insights into how enveloped viruses exploit the host glycans. Full article

Aberrant glycosylation is linked to several diseases, making glycoproteins and their glycoforms promising biomarkers. Traditional methods like mass spectrometry offer high sensitivity but are costly, time-consuming, and unsuitable for point-of-care testing. Electrochemical biosensors emerge as an attractive alternative due to their simplicity, affordability, portability, and rapid response. This review focuses on electrochemical strategies developed to assess the glycosylation level of a specific glycoprotein or biological structure rather than merely glycoprotein or cell concentration, as in previous reviews. Approaches include the use of aptamers, boronic acid derivatives, antibodies, and lectins, often combined with nanomaterials for enhanced sensitivity. Applications span the diagnosis/prognosis of several illnesses such as diabetes, congenital disorders of glycosylation, cancer, and neurodegenerative diseases. Innovative designs incorporate microfluidic and paper-based platforms for faster, low-cost analysis, while strategies using dual-signal acquisition or competitive assays improve accuracy. Despite promising sensitivity and selectivity, most sensors require multi-step protocols and lack of validation in clinical samples. Future research should focus on simplifying procedures, integrating microfluidics, and exploring novel capture or detection probes such as metal complexes or metal–organic frameworks. Overall, electrochemical sensors hold significant potential for point-of-care testing, enabling rapid and precise evaluation of glycosylation status, which could drive cell-based biomarker discovery and disease diagnostics. Full article

Background: In the treatment of ischemic stroke, both tissue-type plasminogen activator (t-PA) thrombolytic and endovascular therapy are employed; however, delayed intervention with these therapies increases the risk of hemorrhage. Hemorrhage associated with delayed t-PA treatment involves the activation of plasmin and matrix metalloproteinases (MMPs); however, the detailed mechanisms underlying I/R activation remain unclear. Objectives: This study examined the effects of delayed recanalization on ischemic stroke in a permanent middle cerebral artery (MCA) occlusion (MCA-O) model, and a novel MCA ischemia/reperfusion (I/R) model: 2-h ischemia followed by reperfusion (I/R 2 h), and 4.5-h ischemia followed by reperfusion (I/R 4.5 h). Secondary induced thrombus (SIT) formation, hemorrhage, MMP activity, MMP-9 immunoreactivity, and tomato lectin (TL) staining, as well as the effects of t-PA and heparin treatment were evaluated. Results: SIT formed within 1 h after reperfusion in the I/R 4.5 h model only, while t-PA or heparin treatment reduced SIT formation. Hemorrhage increased with or without t-PA administration in the I/R 4.5 h model, but it was suppressed by heparin pretreatment. MMP activity and MMP-9 immunoreactivity were localized to the SIT. Additionally, a negative staining area for TL was observed in the damaged area, where SIT formed in the I/R 4.5 h model. Conclusions: These results suggest that delayed recanalization induces SIT via glycocalyx degradation, leading to hemorrhage via plasmin/MMP-9 activation by endogenous and exogenous t-PA-mediated fibrinolysis in novel murine models of ischemic stroke. Furthermore, inhibition of SIT formation is beneficial for suppressing hemorrhages associated with delayed recanalization after endovascular or t-PA therapy. Full article

The effective treatment of aggressive brain tumors, such as glioblastoma, is critically hindered by the blood-brain barrier (BBB) and the non-specific clearance of therapeutic agents by the immune system. Superparamagnetic iron oxide nanoparticles (SPMNPs) offer a powerful theranostic platform, combining magnetic resonance imaging (MRI)-based diagnostics with therapeutic delivery and hyperthermia. However, their clinical translation requires sophisticated strategies to ensure precise delivery to the tumor site. This review examines innovative functionalization strategies to enhance the targeting and efficacy of SPMNPs. Specifically, it addresses the various strategies for coating magnetic nanoparticles with carbohydrates, including both covalent and non-covalent methods, and the subsequent functionalization of these glycoconjugates to exploit the unique biological environment of brain tumors. The use of glycoconjugates on the nanoparticle surface is a key strategy, leveraging the altered glycosylation patterns and overexpression of specific lectins on glioma cell surfaces to achieve highly selective cellular targeting. The review details the synergistic effect achieved by combining these functionalized nanoparticles with external magnetic field guidance. This combination provides a dual-action mechanism: the magnetic field actively guides the nanoparticles across the BBB and concentrates them within the tumor mass, while the carbohydrate coating ensures specific cellular uptake, thereby significantly improving local therapeutic concentration and minimizing systemic toxicity. The scope of this review includes the development and evaluation of carbohydrate-coated SPMNPs, outlining their optimized physicochemical properties for both in vitro and in vivo imaging and treatment of cancerous brain tissues. This comprehensive evaluation represents a critical advancement in biomedicine, aiming to improve the prognosis for patients with brain cancer through more precise and effective therapeutic interventions. Full article

For 12 isolates of Ilyonectria mors-panacis and 4 isolates of Ilyonectria robusta, the number of genes in the secretome showed a negative correlation with growth rates in culture, especially for small secreted non-cysteine-rich and cysteine-rich proteins, and several proteases and lipases, while it was positively correlated with genes for six CAZyme classes/modules and other proteases and lipases. However, this significant correlation with growth rate was influenced by the I. robusta isolates mostly having faster growth rates than the I. mors-panacis isolates on PDA, indicating a species-level difference. The only significant relationship of gene number to virulence was a positive correlation with genes for secreted glycoside hydrolases in families 18 and 78, and this was related to differences between isolates, even if only I. mors-panacis isolates were examined, indicating a difference within species. Glycoside hydrolase family 18 includes chitinase-like proteins, endo-β-N-acetylglucosaminidases, lectins, and xylanase inhibitors, which could help suppress triggered immunity by the host and regulate fungal xylanase activity. Glycoside hydrolase family 78 contain α-L-rhamnosidases that can cleave flavonoid glycosides, saponins, and ginsenosides, which could degrade antimicrobial compounds produced as a host response during infection. These results indicate that the number of certain classes of secreted enzymes could be a factor in both growth rate in culture and virulence. Full article

The spotted knifejaw (Oplegnathus punctatus) has emerged as a species with substantial potential for aquaculture development in China. However, its industrial cultivation is severely constrained by viral diseases. Among these, viral nervous necrosis (VNN), caused by nervous necrosis virus (NNV), represents a critical bottleneck to the sustainable development of this industry. In order to elucidate the immune response mechanisms of the brain cells of spotted knifejaw, this study established a poly (I:C) stimulation model in vitro and performed transcriptomic sequencing to analyze the differentially expressed genes (DEGs) after stimulation. There were 3169, 3228, and 3262 DEGs at 3 h, 6 h, and 12 h compared to 0 h (control), respectively. Co-expression time clustering of DEGs identified two gene clusters (cluster 6 and cluster 10), which included several immune-related genes. GO and KEGG enrichment analyses indicated that DEGs among the four time points were significantly enriched in immune signaling pathways, including the NOD-like receptor, RIG-I-like receptor, C-type lectin receptor, and Toll-like receptor pathways, as well as disease-response pathways. In total, 1398 common DEGs were identified among three comparative groups, which delineated six interaction clusters and 30 hub genes in protein–protein interaction (PPI) network analysis. By integrating a cellular model with transcriptomics, this study provides preliminary insights into the molecular immune mechanisms underlying the response of brain cells to poly (I:C) stimulation, offering important theoretical support for future research on disease-resistant breeding and disease control strategies in spotted knifejaw. Full article