Fucoidans from Laminaria hyperborea (LH) can be antioxidative, antiangiogenic, and anti-inflammatory. In this study, a very high-molecular weight (3700 kDa) fucoidan from LH, FucBB04, was tested regarding its bioactivity in age-related macular degeneration (AMD) models in vitro. Primary retinal pigment epithelium (RPE) from pig eyes, human uveal melanoma cell line OMM-1, and RPE cell line ARPE-19 were used. Substituents of the extract were determined with chemical analysis. Cell viability was tested with tetrazolium assay (MTT), oxidative stress was induced by H2O2 or erastin, respectively. Secreted vascular endothelial growth factor A (VEGF-A) was assessed with ELISA. Retinal pigment epithelium 65 kDa protein (RPE65) and protectin (CD59) protein expression were tested in Western blot. Cell barrier was assessed by measuring trans-epithelial electrical resistance (TEER), phagocytic ability by a fluorescence assay. Gene expression and secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) were tested in real-time PCR and ELISA. FucBB04 displayed no oxidative stress protective effects. Its effect on VEGF was inconsistent, with VEGF secretion reduced in primary RPE, but not in ARPE-19. On the other hand, Lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC)-induced IL-6 or IL-8 secretion was reduced by FucBB04, while complement inhibiting protein CD59 was not affected. In addition, FucBB04 did not influence the gene expression of IL-6 or IL-8. Visual cycle protein RPE65 expression, phagocytic ability, and barrier function were reduced by FucBB04. Very high-molecular weight fucoidan from LH shows bioactivities against AMD-related pathological pathways, but adverse effects on RPE function may limit its suitability as a therapeutic compound. Smaller high-molecular weight fucoidans are recommended for further research.

N-acetylglucosamine (GlcNAc) is involved in diverse signaling pathways in dimorphic yeasts and bacteria and is related to morphogenetic switching, mating, stress, virulence, and cell death. Recently, GlcNAc has been shown to promote plant growth by shaping the bacterial soil community. However, the role of GlcNAc sensing in filamentous soil fungi has not been investigated. By using Trichoderma reesei as a model organism, we show here that GlcNAc impacts the expression of around 2100 genes. Carbohydrate metabolism, amino acid metabolism, and secondary metabolism were the three most strongly affected classes of eukaryotic orthologous groups (KOG classes). Two key regulators of GlcNAc catabolism, the NDT80 domain-containing transcriptional regulator RON1, and a GlcNAc sensor, NGS1, are needed for differential regulation of two-thirds of these genes. In silico structural modeling of NGS1 identified a domain with homology to the GCN5-related histone acetyltransferase from Candida albicans, which serves as a GlcNAc catabolism regulator and GlcNAc sensor. Finally, we characterized the third regulator of GlcNAc sensing in T. reesei, which is the highly specific GlcNAc transporter N-acetylglucosamine transporter (NGT1). Using a deletion mutant of ngt1, we demonstrate that GlcNAc has to enter the cell to activate the GlcNAc catabolic gene expression. Interestingly, in contrast to dimorphic yeasts, the pathways for defense and pathogenicity seem to be induced in T. reesei by external GlcNAc. Given the ancestral role of Trichoderma spp. in the fungal kingdom and the highly conserved GlcNAc catabolism cluster that includes their regulators in many species of fungi, we propose a regulatory network for GlcNAc sensing in soil fungi.

The use of plastics, valued for its affordability, durability, and convenience, has grown significantly with the advancement of industry. Paradoxically, these very properties of plastics have also led to significant environmental challenges. Plastics are highly resistant to decomposition, resulting in their accumulation on land, where they eventually enter aquatic environments, due to natural processes or human activities. Among these plastics, microplastics, which are tiny plastic particles, are particularly concerning when they enter aquatic ecosystems, including rivers and seas. Their small size makes them easily ingestible by aquatic organisms, either by mistake or through natural feeding behaviors, which poses serious risks. Moreover, microplastics readily adsorb other pollutants present in aquatic environments, creating pollutant complexes that can have a synergistic impact, magnifying their harmful effects compared to microplastics or pollutants acting alone. As a result, extensive research has focused on understanding the effects of microplastics on aquatic organisms. Numerous studies have demonstrated that aquatic organisms exposed to microplastics, either alone or in combination with other pollutants, exhibit abnormal hatching, development, and growth. Additionally, many genes, particularly those associated with the antioxidant system, display abnormal expression patterns in these conditions. In this review, we examine these impacts, by discussing specific studies that explore changes in phenotype and gene expression in aquatic organisms exposed to microplastics, both independently and in combination with adsorbed pollutants.

Fungal cell walls are dynamic extracellular matrices that enable efficient adaptation to changing environments. While the cell wall compositions of yeasts, human, and plant pathogenic fungi have been studied to some extent, the cell walls of mycoparasites remain poorly characterized. Trichoderma species comprise a diverse group of soil fungi with different survival strategies and lifestyles. The comparative study of cell wall carbohydrate-active enzymes in 13 Trichoderma spp. revealed that the types of enzymes involved in chitin and chitosan metabolism are phylogenetically distant between mycoparasitic and saprotrophic species. Here, we compare the carbohydrate composition and function of the cell wall of a saprotrophic strain Trichoderma reesei with that of the mycoparasitic, biological control agent Trichoderma atroviride. Monosaccharide and glycosidic linkage analyses as well as dual in situ interaction assays showed that the cell wall polysaccharide composition is conserved between both species, except for the amounts of chitin detected. The results suggest that the observed accumulation of chitosan during mycoparasitism may prevent host recognition. Remarkably, Trichoderma atroviride undergoes dynamic cell wall adaptations during both vegetative development and mycoparasitism, which appears to be confirmed by an evolutionarily expanded group of specialized enzymes. Overall, our analyses support the notion that habitat specialization is reflected in cell wall architecture and that plastic chitin remodeling may confer an advantage to mycoparasites, ultimately enabling the successful invasion and parasitism of plant pathogens. This information may potentially be exploited for the control of crop diseases using biological agents.

Vibrio species pose significant threats worldwide, causing mortalities in aquaculture and infections in humans. Global warming and the emergence of worldwide strains of Vibrio diseases are increasing day by day. Control of Vibrio species requires effective monitoring, diagnosis, and treatment strategies at the global scale. Despite current efforts based on chemical, biological, and mechanical means, Vibrio control management faces limitations due to complicated implementation processes. This review explores the intricacies and challenges of Vibrio-related diseases, including accurate and cost-effective diagnosis and effective control. The global burden due to emerging Vibrio species further complicates management strategies. We propose an innovative integrated technology model that harnesses cutting-edge technologies to address these obstacles. The proposed model incorporates advanced tools, such as biosensing technologies, the Internet of Things (IoT), remote sensing devices, cloud computing, and machine learning. This model offers invaluable insights and supports better decision-making by integrating real-time ecological data and biological phenotype signatures. A major advantage of our approach lies in leveraging cloud-based analytics programs, efficiently extracting meaningful information from vast and complex datasets. Collaborating with data and clinical professionals ensures logical and customized solutions tailored to each unique situation. Aquaculture biotechnology that prioritizes sustainability may have a large impact on human health and the seafood industry. Our review underscores the importance of adopting this model, revolutionizing the prognosis and management of Vibrio-related infections, even under complex circumstances. Furthermore, this model has promising implications for aquaculture and public health, addressing the United Nations Sustainable Development Goals and their development agenda.

The phylum Oomycota contains economically important pathogens of animals and plants, including Saprolegnia parasitica , the causal agent of the fish disease saprolegniasis. Due to intense fish farming and banning of the most effective control measures, saprolegniasis has re-emerged as a major challenge for the aquaculture industry. Oomycete cells are surrounded by a polysaccharide-rich cell wall matrix that, in addition to being essential for cell growth, also functions as a protective “armor.” Consequently, the enzymes responsible for cell wall synthesis provide potential targets for disease control. Oomycete cell wall biosynthetic enzymes are predicted to be plasma membrane proteins. To identify these proteins, we applied a quantitative (iTRAQ) mass spectrometry-based proteomics approach to the plasma membrane of the hyphal cells of S. parasitica , providing the first complete plasma membrane proteome of an oomycete species. Of significance is the identification of 65 proteins enriched in detergent-resistant microdomains (DRMs). In silico analysis showed that DRM-enriched proteins are mainly involved in molecular transport and β-1,3-glucan synthesis, potentially contributing to pathogenesis. Moreover, biochemical characterization of the glycosyltransferase activity in these microdomains further supported their role in β-1,3-glucan synthesis. Altogether, the knowledge gained in this study provides a basis for developing disease control measures targeting specific plasma membrane proteins in S. parasitica . The significance of this research lies in its potential to combat saprolegniasis, a detrimental fish disease, which has resurged due to intensive fish farming and regulatory restrictions. By targeting enzymes responsible for cell wall synthesis in Saprolegnia parasitica , this study uncovers potential avenues for disease control. Particularly noteworthy is the identification of several proteins enriched in membrane microdomains, offering insights into molecular mechanisms potentially involved in pathogenesis. Understanding the role of these proteins provides a foundation for developing targeted disease control measures. Overall, this research holds promise for safeguarding the aquaculture industry against the challenges posed by saprolegniasis.

The significance of this research lies in its potential to combat saprolegniasis, a detrimental fish disease, which has resurged due to intensive fish farming and regulatory restrictions. By targeting enzymes responsible for cell wall synthesis in Saprolegnia parasitica , this study uncovers potential avenues for disease control. Particularly noteworthy is the identification of several proteins enriched in membrane microdomains, offering insights into molecular mechanisms potentially involved in pathogenesis. Understanding the role of these proteins provides a foundation for developing targeted disease control measures. Overall, this research holds promise for safeguarding the aquaculture industry against the challenges posed by saprolegniasis.

Barley (1,3;1,4)-β-d-glucanase is believed to have evolved from an ancestral monocotyledon (1,3)-β-d-glucanase, enabling the hydrolysis of (1,3;1,4)-β-d-glucans in the cell walls of leaves and germinating grains. In the present study, we investigated the substrate specificities of variants of the barley enzymes (1,3;1,4)-β-d-glucan endohydrolase [(1,3;1,4)-β-d-glucanase] isoenzyme EII (HvEII) and (1,3)-β-d-glucan endohydrolase [(1,3)-β-d-glucanase] isoenzyme GII (HvGII) obtained by protein segment hybridization and site-directed mutagenesis. Using protein segment hybridization, we obtained three variants of HvEII in which the substrate specificity was that of a (1,3)-β-d-glucanase and one variant that hydrolyzed both (1,3)-β-d-glucans and (1,3;1,4)-β-d-glucans; the wild-type enzyme hydrolyzed only (1,3;1,4)-β-d-glucans. Using substitutions of specific amino acid residues, we obtained one variant of HvEII that hydrolyzed both substrates. However, neither protein segment hybridization nor substitutions of specific amino acid residues gave variants of HvGII that could hydrolyze (1,3;1,4)-β-d-glucans; the wild-type enzyme hydrolyzed only (1,3)-β-d-glucans. Other HvEII and HvGII variants showed changes in specific activity and their ability to degrade the (1,3;1,4)-β-d-glucans or (1,3)-β-d-glucans to larger oligosaccharides. We also used molecular dynamics simulations to identify amino-acid residues or structural regions of wild-type HvEII and HvGII that interact with (1,3;1,4)-β-d-glucans and (1,3)-β-d-glucans, respectively, and may be responsible for the substrate specificities of the two enzymes.

Cellular genome is considered a dynamic blueprint of a cell since it encodes genetic information that gets temporally altered due to various endogenous and exogenous insults. Largely, the extent of genomic dynamicity is controlled by the trade-off between DNA repair processes and the genotoxic potential of the causative agent (genotoxins or potential carcinogens). A subset of genotoxins form DNA adducts by covalently binding to the cellular DNA, triggering structural or functional changes that lead to significant alterations in cellular processes via genetic (e. g., mutations) or non-genetic (e. g., epigenome) routes. Identification, quantification, and characterization of DNA adducts are indispensable for their comprehensive understanding and could expedite the ongoing efforts in predicting carcinogenicity and their mode of action. In this review, we elaborate on using Artificial Intelligence (AI)-based modeling in adducts biology and present multiple computational strategies to gain advancements in decoding DNA adducts. The proposed AI-based strategies encompass predictive modeling for adduct formation via metabolic activation, novel adducts’ identification, prediction of biochemical routes for adduct formation, adducts’ half-life predictions within biological ecosystems, and, establishing methods to predict the link between adducts chemistry and its location within the genomic DNA. In summary, we discuss some futuristic AI-based approaches in DNA adduct biology.

The limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 µg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 µmol/L, while LDT537 showed IC50 values of 29.12 µmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.