Search Results (617)

Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly from tissue, including formalin-fixed paraffin-embedded (FFPE) specimens. In this context, MALDI matrix selection is crucial for lipid extraction and ionization, influencing key aspects such as molecular coverage and sensitivity, especially in such specimens with already depleted lipid content. Thus, in this work, we aim to explore the feasibility of mapping lipid species in FFPE clinical samples with MALDI-MSI using 6-aza-2-thiothymine (ATT) as a matrix of choice. Methods: To do so, ATT performances were first compared to those two other matrices commonly used for lipidomic analyses, 2′,5′-dihydroxybenzoic acid (DHB) and Norharmane (NOR), on lipid standards. Results: As a proof-of-concept, we then assessed ATT’s performance for the MALDI-MSI analysis of lipids in FFPE brain sections, both in positive and negative ion modes, comparing results with those obtained from other commonly used dual-polarity matrices. In this context, ATT enabled the putative annotation of 98 lipids while maintaining a well-balanced detection of glycerophospholipids (60.2%) and sphingolipids (32.7%) in positive ion mode. It outperformed both DHB and NOR in the identification of glycolipids (3%) and fatty acids (4%). Additionally, ATT exceeded DHB in terms of total lipid count (62 vs. 21) and class diversity and demonstrated performance comparable to NOR in negative ion mode. Moreover, ATT was applied to a FFPE glioblastoma tissue microarray (TMA) evaluating the ability of this matrix to reveal biologically relevant lipid features capable of distinguishing normal brain tissue from glioblastoma regions. Conclusions: Altogether, the results presented in this work suggest that ATT is a suitable matrix for pathology imaging applications, even at higher lateral resolutions of 20 μm, not only for proteomic but also for lipidomic analysis. This could enable the use of the same matrix type for the analysis of both lipids and peptides on the same tissue section, offering a unique strategic advantage for multi-omics studies, while also supporting acquisition in both positive and negative ionization modes. Full article

The cosmetics industry has been seeking to develop products with renewable natural ingredients to reduce the use of or even replace synthetic substances. Biosurfactants can help meet this demand. These natural compounds are renewable, biodegradable, and non-toxic or have low toxicity, offering minimal risk to humans and the environment, which has attracted the interest of an emerging consumer market and, consequently, the cosmetics industry. The aim of the present study was to produce a biosurfactant from the yeast Starmerella bombicola ATCC 22214 cultivated in a mineral medium containing 10% soybean oil and 5% glucose. The biosurfactant reduced the surface tension of water from 72.0 ± 0.1 mN/m to 33.0 ± 0.3 mN/m after eight days of fermentation. The yield was 53.35 ± 0.39 g/L and the critical micelle concentration was 1000 mg/L. The biosurfactant proved to be a good emulsifier of oils used in cosmetic formulations, with emulsification indices ranging from 45.90 ± 1.69% to 68.50 ± 1.10%. The hydrophilic–lipophilic balance index demonstrated the wetting capacity of the biosurfactant and its tendency to form oil-in-water (O/W) emulsions, with 50.0 ± 0.20% foaming capacity. The biosurfactant did not exhibit cytotoxicity in the MTT assay or irritant potential. Additionally, an antioxidant activity of 58.25 ± 0.32% was observed at a concentration of 40 mg/mL. The compound also exhibited antimicrobial activity against various pathogenic microorganisms. The characterisation of the biosurfactant using magnetic nuclear resonance and Fourier transform infrared spectroscopy revealed that the biomolecule is a glycolipid with an anionic nature. The results demonstrate that biosurfactant produced in this work has potential as an active biotechnological ingredient for innovative, eco-friendly cosmetic formulations. Full article

Human applications of surfactants have been diverse, from their initial use as detergents to their subsequent utilization in a multitude of other fields, including medicine, lubricants, cosmetics, and even assisted oil recovery. Nevertheless, the most significant challenge lies in the synthesis of surfactants. A particular challenge is the purification of compounds following chemical synthesis, as well as the toxic effect of the solvents used. Consequently, there is a growing need for more environmentally friendly solutions, namely solvents that are less toxic and more biocompatible, as well as reactions in which an enzyme serves as a catalyst. This review examines the various methods of synthesizing sugar esters and glycolipids, evaluating their respective advantages and disadvantages. Full article

Galectin-3 (Gal-3) is a β-galactoside-binding lectin that mediates diverse signaling events in multiple cell types, including immune cells. It is also a prognostic indicator for multiple clinically important disorders, including cardiovascular disease. Gal-3 binds to cell surface glycans to form lattices that modulate surface receptor signaling and internalization. However, the tissue-specific regulation of Gal-3 surface expression remains poorly understood. Here, we review evidence for the involvement of Gal-3 in cell surface signaling, intranuclear events, and intracellular trafficking. Our focus will be on the O-GlcNAc modification as a regulator of Gal-3 biosynthesis, non-canonical secretion, and recycling. We argue that the nutrient-driven cytoplasmic hexosamine biosynthetic pathway (HBP) and endomembrane transport mechanisms generate unique pools of nucleotide sugars. The differing levels of nucleotide sugars in the cytosol, endoplasmic reticulum (ER), and Golgi apparatus generate differential thresholds for the responsiveness of O-GlcNAc cycling, N- and O-linked glycan synthesis/branching, and glycolipid synthesis. By regulating Gal-3 synthesis and non-canonical secretion, O-GlcNAc cycling may serve as a nexus constraining Gal-3 cell surface expression and lattice formation. This homeostatic feedback mechanism would be critical under conditions where extensive glycan synthesis and branching in the endomembrane system and on the cell surface are maintained by elevated hexosamine synthesis. Thus, O-GlcNAc cycling and Gal-3 synergize to regulate Gal-3 secretion and influence cellular signaling. In humans, Gal-3 serves as an early-stage prognostic indicator for heart disease, kidney disease, viral infection, autoimmune disease, and neurodegenerative disorders. Since O-GlcNAc cycling has also been linked to these pathologic states, exploring the interconnections between O-GlcNAc cycling and Gal-3 expression and synthesis is likely to emerge as an exciting area of research. Full article

Rouxiella badensis DSM 100043^T had been previously proven to produce a novel glucoselipid biosurfactant which has a very low critical micelle concentration (CMC) as well as very good stability against a wide range of pH, temperature, and salinity. In this study, we performed a function-based library screening from a R. badensis DSM 100043^T genome library to identify responsible genes for biosynthesis of this glucoselipid. The identified open reading frames (ORFs) were cloned into several constructs in Escherichia coli for gene permutation analysis and the individual products were analyzed using high-performance thin-layer chromatography (HPTLC). Products of interest from positive expression strains were purified and analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and nuclear magnetic resonance (NMR) for further structure elucidation. Function-based screening of 5400 clones led to the identification of an operon containing three ORFs encoding acetyltransferase GlcA (ORF1), acyltransferase GlcB (ORF2), and phosphatase/HAD GlcC (ORF3). E. coli pCAT2, with all three ORFs, resulted in the production of identical R. badensis DSM 100043^T glucosedilipid with Glu-C_10:0-C_12:1 as the main congener. ORF2-deletion strain E. coli pAFP1 primarily produced glucosemonolipids, with Glu-C_10:0,3OH and Glu-C_12:0 as the major congeners, predominantly esterified at the C-2 position of the glucose moiety. Furthermore, fed-batch bioreactor cultivation of E. coli pCAT2 using glucose as the carbon source yielded a maximum glucosedilipid titer of 2.34 g/L after 25 h of fermentation, which is 55-fold higher than that produced by batch cultivation of R. badensis DSM 100043^T in the previous study. Full article

Significant wastes such as bagasse, molasses, and vinasses are produced during sugarcane processing. Due to their high sugar content, these wastes are commonly used as low-cost substrates for biofuel production. However, these substrates are also suitable for the microbial synthesis of high-value biochemicals like biosurfactants. Sporisorium scitamineum, a smut fungus capable of growing on sugarcane residues and producing mannosylerythritol lipids (MELs) and cellobiose lipids (CBLs), was identified as a promising candidate for valorizing sugarcane wastes. This study investigated MEL and CBL co-production from pure sugars and sugarcane molasses using an S. scitamineum strain isolated from sugarcane residues originating from KwaZulu-Natal, South Africa. Among the sugars tested, sucrose supported the highest glycolipid production, yielding 0.24 g/L MELs and 2.73 g/L CBLs. Lower titers were achieved with fructose, and no production occurred with glucose. Sugarcane molasses also proved to be an effective substrate, yielding 1.46 g/L CBLs—the highest reported titer from an industrial waste to date. However, all titers remained far below those of other glycolipids, which consistently exceed 50 g/L. Future efforts should focus on enhancing CBL production through process optimization or genetic engineering. Full article

Nitrite is a common pollutant in aquaculture systems and can pose serious threats to fish health, especially under high-temperature conditions. This study aimed to investigate the impact of nitrite stress on the growth, glycolipid metabolism, and hepatic metabolomic profiles in the spotted seabass fry (Lateolabrax maculatus) under elevated temperature conditions at 33 °C. A total of 450 fish (28.52 ± 0.84 g) were randomly distributed into nine tanks and exposed to three nitrite concentrations (0, 8, and 16 mg/L), with samples collected on days 1, 3, 7, 14, 21, and 28. Results showed that higher nitrite levels significantly reduced final body weight, weight gain, survival rate, hepatosomatic index, and viscerosomatic index. Blood glucose and triglyceride levels, whole-body crude lipid, liver total cholesterol, and hepatic glycogen content also declined significantly under higher nitrite stress. In contrast, hepatic lactate and lactate dehydrogenase increased in the high-nitrite group. Gene expression analysis revealed suppressed lipid synthesis and enhanced lipolysis under nitrite exposure. Metabolomic analysis further demonstrated disruptions in key energy-related pathways, including the TCA cycle, pentose phosphate pathway, and insulin signaling. These findings indicate that nitrite stress impairs growth and energy metabolism in spotted seabass, which respond by mobilizing energy reserves to cope with combined stress of high temperature and nitrite. Full article

Mannosyl erythritol lipids (MELs) are glycolipid biosurfactants produced by Ustilaginomycete yeasts. The MEL biosynthetic pathway has been characterized in Ustilago maydis where a putative transporter encoded by MMF1 is required for the secretion of the glycolipid surfactant to the extracellular space. The anamorphic yeast Moesziomyces antarcticus is a prolific producer of MELs, but the mechanism of MEL secretion is less well characterized than in U. maydis. Homologous recombination was employed to generate a disruption of the MMF1 gene in M. antarcticus JCM10317. This mutation did not prevent the intracellular accumulation of MEL species but did result in significantly reduced secretion of the conventional MEL-A, MEL-B and MEL-C species detectable by thin-layer chromatography. However, the mutant strain did secrete a glycolipid species that is distinct from conventional MEL-A/B/C and similar to a glycolipid secreted by MMF1 mutant strains of U. maydis and Pseudozyma tsukubaensis. Despite the defect in MEL secretion displayed by the M. antarcticus strain harbouring a disrupted MMF1 gene, these cells did not display a significant defect in growth or cell morphology. The findings of this investigation provide evidence that M. antarcticus MMF1 encodes a transporter required for the secretion of MELs but not required for MEL synthesis or cell growth. Full article

Biorefinery is gaining attention as a promising approach to valorize natural resources and promote a circular bioeconomy. This study aimed to recover high-value molecules, such as xanthophylls and polar lipids with nutraceutical applications, through enzymatic pretreatment and sequential pressurized liquid extraction (PLEseq), by reusing the residual biomass of Nannochloropsis gaditana after each processing step. Remarkably, pure glycolipids (102.95 ± 1.10 mg g⁻¹ dry weight) were obtained immediately after enzymatic pretreatment, facilitating their easy recovery. Furthermore, two alternative sequential extraction processes were successfully developed, using ethanol and water as green solvents at varying temperatures and in different orders. The most effective PLEseq conditions yielded up to 48 mg mL⁻¹ of carbohydrates using water at 50 °C, and up to 44 mg mL⁻¹ of proteins via subcritical water extraction at 100 °C, prior to conventional lipid extraction with ethanol to produce various concentrated extracts. In the inverted PLEseq process—starting with ethanol extraction followed by successive water washes—isolated and purified fractions of lutein and astaxanthin were obtained, contributing to the complete depletion of the residual biomass. Overall, the development of an integrated and sequential biorefinery protocol that enables the extraction of multiple high-value compounds holds significant potential for application in the food industry. Full article

β-Lactosylceramide (β-LacCer) is not only a key intermediate in the biosynthesis of complex glycosphingolipids (GSLs) but also an important regulator of many biological processes. To facilitate the investigation of β-LacCer and other GSLs, a series of β-LacCer analogs with an azido group at the 6-C-position of the D-galactose in lactose and varied forms of the ceramide moiety were synthesized from commercially available lactose in sixteen linear steps by a versatile and diversity-oriented strategy, which engaged lipid remodeling and glycan functionalization at the final stage. These azide-labeled β-LacCer analogs are flexible and universal platforms that are suitable for further functionalization with other molecular tags via straightforward and biocompatible click chemistry, thereby paving the way for their application to various biological studies. Full article

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by the pathological accumulation of amyloid-β plaques and tau neurofibrillary tangles, both of which disrupt neuronal communication and function. Emerging evidence highlights the role of extracellular vesicles (EVs) as key mediators of intercellular communication, particularly in the propagation of pathological proteins in AD. Among the regulatory factors influencing EV composition and function, neuraminidase 1 (NEU1), a lysosomal sialidase responsible for desialylating glycoproteins has gained attention for its involvement in EV glycosylation. This review explores the role of NEU1 in modulating EV glycosylation, with particular emphasis on its influence on immune modulation and intracellular trafficking pathways and the subsequent impact on intercellular signaling and neurodegenerative progression. Altered NEU1 activity has been associated with abnormal glycan profiles on EVs, which may facilitate the enhanced spread of amyloid-β and tau proteins across neural networks. By regulating glycosylation, NEU1 influences EV stability, targeting and uptake by recipient cells, primarily through the desialylation of surface glycoproteins and glycolipids, which alters the EV charge, recognition and receptor-mediated interactions. Targeting NEU1 offers a promising therapeutic avenue to restore EV homeostasis and reduces pathological protein dissemination. However, challenges persist in developing selective NEU1 inhibitors and effective delivery methods to the brain. Furthermore, altered EV glycosylation patterns may serve as potential biomarkers for early AD diagnosis and monitoring. Overall, this review highlights the importance of NEU1 in AD pathogenesis and advocates for deeper investigation into its regulatory functions, with the aim of advancing therapeutic strategies and biomarker development for AD and related neurological disabilities. Full article

Background/Objectives: Diabetic retinopathy is an ocular disease caused by changes in the expression of inflammatory mediators and increased oxidative stress in the retina and is the leading cause of vision loss in diabetic patients. Currently, there is no treatment capable of reversing retinal damage, which represents a significant burden on the quality of life of patients. (1R)-1-Dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin stands outs as a prototype of the sp²-iminoglycolipids family for its beneficial neuroprotective effect against this chronic eye disease. Critical issues related to the low solubility and bioavailability of this glycolipid in biological settings are overcome by its encapsulation in a Zeolitic-Imidazolate Framework (ZIF) structure, resulting in homogeneous and biocompatible GlycoZIF nanoparticles. Cell studies show an enhanced cellular uptake compared with the free glycolipid, and importantly, its bioactivity is preserved once released inside cells. Methods: Extensive in vitro and ex vivo assays with diabetic retinopathy models unveil the mechanistic pathways of the designed GlycoZIF. Results: A reduction in proinflammatory mediators, increased heme oxygenase-1 level, inhibition of NLRP3 inflammasome, and reduced reactive gliosis is shown. Conclusions: These findings demonstrate for the first time the potential of Glyco-modified ZIFs for the treatment of diabetes-related ocular problems by controlling the immune-mediated inflammatory response. Full article

Cell membranes contain a variety of biomolecules, especially various kinds of lipids and proteins, which constantly change with fluidity and environmental stimuli. Though Helfrich curvature elastic energy has successfully explained many phenomena for single-component membranes, a new theoretical framework for multicomponent membranes is still a challenge. In this work, we propose a generalized Helfrich free-energy functional describe equilibrium shapes and phase behaviors related to membrane heterogeneity with via curvature-component coupling in a unified framework. For multicomponent membranes, a new but important Laplace–Beltrami operator is derived from the variational calculation on the integral of Gaussian curvature and applied to explain the spontaneous nanotube formation of an asymmetric glycolipid vesicle. Therefore, our general mathematical framework shows a predictive capabilities beyond the existing multicomponent membrane models. The set of new curvature-component coupling EL equations have been derived for global vesicle shapes associated with the composition redistribution of multicomponent membranes for the first time and specified into several typical geometric shape equations. The equilibrium radii of isotonic vesicles for both spherical and cylindrical geometries are calculated. The analytical solution for isotonic vesicles reveals that membrane stability requires distinct elastic moduli among components ($k_{\mathrm{A}}\ne k_{\mathrm{B}}$, ${\overline{k}}_{\mathrm{A}}\ne {\overline{k}}_{\mathrm{B}}$), which is consistent with experimental observations of coexisting lipid domains. Furthermore, we elucidate the biophysical implications of the derived shape equations, linking them to experimentally observed membrane remodeling processes. Our new free-energy framework provides a baseline for more detailed microscopic membrane models. Full article

Mulberry (Morus alba) twigs and leaves, rich in flavonoids, polyphenols, polysaccharides, and alkaloids with multi-target regulatory properties on glucose/lipid metabolism, were evaluated for their anti-obesity effects using methanol-extracted twigs (MTE) and aqueous-extracted leaves (MLE) in high-fat diet (HFD)-induced obese mice. Both extracts significantly ameliorated obesity-related metabolic dysregulation, as evidenced by attenuated body weight gain, visceral fat accumulation, serum lipid profiles, homeostatic model assessment of insulin resistance (HOMA-IR), and hepatic inflammation compared to HFD controls (p < 0.05). Concurrently, MTE and MLE enhanced systemic antioxidant capacity and elevated high-density lipoprotein cholesterol (HDL-C) levels. Notably, high-dose MTE (MTEH, 1000 mg/kg) markedly reduced perirenal adiposity while increasing brown adipose tissue mass (p < 0.05). Mechanistic investigations revealed that MTEH reshaped gut microbiota composition by suppressing Firmicutes and Enterococcus, while enriching beneficial Faecalibaculum and Bifidobacterium spp. (p < 0.05). Furthermore, cecal short-chain fatty acid (SCFA) profiling demonstrated MTEH and MLEH-mediated metabolic reprogramming, characterized by increased propionic acid and decreased butyric acid, suggesting microbiota-dependent modulation of host energy metabolism. These findings collectively highlight the potential of mulberry extracts as multi-targeted nutraceuticals for obesity intervention via gut microbiota–SCFA axis regulation. Full article

Microalgae are a subject of interest not only for fundamental research but for various biotechnological applications as well. In this study, the ability of newly isolated strains, i.e., Picochlorum costavermella VAS2.5, Picochlorum oklahomense SAG4.4, Microchloropsis gaditana VON5.3, and Nephroselmis pyriformis PAT2.7, to grow when cultured in an open raceway pond under laboratory conditions and produce various metabolites of high-added value was evaluated. N. pyriformis PAT2.7 and P. costavermella VAS2.5 were the greatest in biomass production (exceeding 0.4 g/L), while P. costavermella VAS2.5 and M. gaditana VON5.3 were the greatest in lipid production (reaching approximately 18%, wt/wt). The lipid fraction of glycolipids and sphingolipids was predominant (43.6–55.4%, wt/wt), followed by neutral lipids (27.1–50.1%, wt/wt) and phospholipids (6.9–17.4%, wt/wt). Picochlora and M. gaditana VON5.3 lipids were rich in ^{Δ5,8,11,14,17}C20:5 and/or ^Δ9,12,15C18:3, while N. pyriformis PAT2.7 synthesized ^Δ9C16:1 in large quantities (30–40%, wt/wt). All strains showed remarkable yields in polysaccharide and protein production, demonstrated a well-balanced amino acid profile, and synthesized pigments in amounts comparable to other studies. The biochemical profiles of these strains showcased their suitability for use primarily in the aquaculture sector. Full article