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Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids (GPLs), and sterols, in Rhizopus delemar 99-880, a well-characterized reference strain among Mucorales. Using shotgun lipidomics as well as liquid- and gas-chromatography-based mass spectrometric analyses, we identified the lipid intermediates and elucidated the biosynthetic pathways of SLs, PGLs, and sterols. The acidic SLs were not found, probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides, as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatdylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of R. delemar 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms.

Ergosterol is essential for fungal cell membrane integrity and growth, and numerous antifungal drugs target ergosterol. Inactivation or modification of ergosterol biosynthetic genes can lead to changes in antifungal drug susceptibility, filamentation and stress response. Here, we found that the ergosterol biosynthesis gene ERG251 is a hotspot for point mutations during adaptation to antifungal drug stress within two distinct genetic backgrounds of Candida albicans. Heterozygous point mutations led to single allele dysfunction of ERG251 and resulted in azole tolerance in both genetic backgrounds. This is the first known example of point mutations causing azole tolerance in C. albicans. Importantly, single allele dysfunction of ERG251 in combination with recurrent chromosome aneuploidies resulted in bona fide azole resistance. Homozygous deletions of ERG251 caused increased fitness in low concentrations of fluconazole and decreased fitness in rich medium, especially at low initial cell density. Homozygous deletions of ERG251 resulted in accumulation of ergosterol intermediates consistent with the fitness defect in rich medium. Dysfunction of ERG251, together with FLC exposure, resulted in decreased accumulation of the toxic sterol (14-ɑ-methylergosta-8,24(28)-dien-3β,6α-diol) and increased accumulation of non-toxic alternative sterols. The altered sterol composition of the ERG251 mutants had pleiotropic effects on transcription, filamentation, and stress responses including cell membrane, osmotic and oxidative stress. Interestingly, while dysfunction of ERG251 resulted in azole tolerance, it also led to transcriptional upregulation of ZRT2, a membrane-bound Zinc transporter, in the presence of FLC, and overexpression of ZRT2 is sufficient to increase azole tolerance in wild-type C. albicans. Finally, in a murine model of systemic infection, homozygous deletion of ERG251 resulted in decreased virulence while the heterozygous deletion mutants maintain their pathogenicity. Overall, this study demonstrates that single allele dysfunction of ERG251 is a recurrent and effective mechanism of acquired azole tolerance. We propose that altered sterol composition resulting from ERG251 dysfunction mediates azole tolerance as well as pleiotropic effects on stress response, filamentation and virulence.

The aim of this study was to determine the influence of the nut roasting process (conventional and microwave methods) and long-term storage (12 months) on phytosterol content and stability. This study was conducted using hazelnuts (Corylus avellana), common walnuts (Juglans regia L.), and shelled peanuts (Arachis hypogaea L.). Two roasting methods were examined: conventional (temp. 170 °C, roasting time 10–20 min.) and microwave (temp. 60 °C, pressure 40 hPa, roasting time 140–180 s). In the studied nuts (raw, roasted and stored), five main types of phytosterols were identified: campesterol, stigmasterol, ß-sitosterol, delta 5-avenasterol and cycloartenol. It was shown that the microwave roasting method caused a two-fold decrease in sterol loss compared with conventional roasting. Moreover, the long-term storage of roasted walnuts using the microwave method showed double the amount of sterols preserved compared with those roasted using the conventional method. The amount of ß-sitosterol, which was the most stable during roasting, depended more on storage duration than on roasting process. The cycloartenol content in the roasted nuts did not depend on storage duration. The sterols present in nuts, raw or roasted using either method, transform more during the first 6 months of storage. [ABSTRACT FROM AUTHOR]

To explore the impact of gamma irradiation on the physicochemical properties and micronutrient contents of tiger nut oil (TNO), tiger nuts were irradiated at 0, 2, 4, 6 and 8 kGy and stored for 0 and 90 days. The physicochemical indexes, fatty acids, and the contents of tocopherols, sterols and phospholipids in TNO were identified and the structure was analyzed by FTIR. The results revealed that irradiation had no significant influence on the fatty acids of TNO, but increased its physicochemical indexes. Also, bioactive constituents, for instance, tocopherols and carotenoids, decreased with increasing irradiation dose. The phospholipid content increased with irradiation dose, but total sterols increased only at an irradiation dose of 2 kGy. FTIR confirmed that irradiation disrupted the structure of triacylglyceride, exhibiting a minor change in peaks at 3007, 2925, 2855, 1158, 1094 and 1032 cm− 1. After 90 days of storage, both irradiated and unirradiated samples showed similar deterioration in oil quality indices compared to the initial storage period. It is recommended that gamma irradiation of tiger nuts should be limited to less than 2 kGy. [ABSTRACT FROM AUTHOR]

The composition of eukaryotic membranes reflects a varied but precise amalgam of lipids. The genetic underpinning of how such diversity is achieved or maintained is surprisingly obscure, despite its clear metabolic and pathophysiological impact. The Arv1 protein is represented in all eukaryotes and was initially identified in the model eukaryote Sacccharomyces cerevisiae as a candidate transporter of lipids from the endoplasmic reticulum. Human Arv1 has been shown to directly bind cholesterol and fatty acid affinity probes. Murine in vivo studies point to a role for ARV1 in regulating obesity, glucose tolerance, insulin sensitivity and brain function. Multiple human ARV1 variants have been associated with epileptic encephalopathy, cerebellar ataxia, and severe intellectual deficits. We hypothesize that Arv1 acts as an energy independent, lipid scramblase at the endoplasmic reticulum thereby modulating membrane lipid asymmetry and thus the trafficking of sterols and the substituents of glycosyl-phosphatidylinositol and sphingolipid biosynthesis. [ABSTRACT FROM AUTHOR]

The genus Amsonia, a member of the Apocynaceae family, comprises plants with notable medicinal benefits. In 2022 and 2023, Amsonia tabernaemontana Walt. seeds introduced to Bulgaria were collected and analyzed. Given the limited information available on the chemical composition of A. tabernaemontana, this study aimed to evaluate the phytochemical profile of the plant seeds collected over two consecutive years. Although members of the genus Amsonia are not conventional oilseed crops, the glyceride oil content was 7.8% and 11.1% in the respective samples. The chemical composition was meticulously analyzed, revealing carbohydrates in the largest amounts (60.4% and 61.3%), with crude fibers at 18.3% and 24.8%, and protein content at 19.5% and 13.0%. The amounts of ash and moisture content were also quantified. Additionally, the fatty acids, sterols, tocopherols, and phospholipids of the seed oil were examined. β-Sitosterol emerged as the main component in both harvests. The total tocopherol content was relatively low (52.7 mg/kg vs. 20.0 mg/kg), with α-tocopherol being predominant. Phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine were identified as the principal components of the phospholipid fraction. The fatty acid composition primarily included linoleic (61.0 and 61.2%) and oleic acids (28.7 and 28.6%). [ABSTRACT FROM AUTHOR]

Background Scedosporium/Lomentospora species are ranked as the second most frequently isolated filamentous fungi from cystic fibrosis (CF) patients. Previously, we demonstrated that the minimum inhibitory concentration (MIC) for voriconazole and posaconazole increased when performed on a mucin-containing synthetic CF sputum medium (SCFM) compared to the standard medium, RPMI-1640. In this study, we have expanded the MIC comparison to four additional azoles and investigated characteristics linked to azole resistance in Scedosporium apiospermum , Scedosporium minutisporum , Scedosporium aurantiacum and Lomentospora prolificans. Methods MIC was assayed by CLSI protocol, efflux pump activity was assessed by rhodamine 6G and sterols were analysed by gas chromatography-mass spectrometry (GC-MS). Results Overall, MICs for fluconazole, itraconazole, voriconazole, posaconazole, miconazole and ketoconazole increased by least 2-fold when susceptibility tests were performed using SCFM compared to RPMI. The activity of efflux pumps was similar in both media; however, in RPMI, but not in SCFM, the activity was induced by voriconazole and fluconazole. Additionally, MICs for those antifungals decreased more noticeably in SCFM than in RPMI in the presence of the efflux pump inhibitor PaβN. The SCFM-grown cells presented fewer sterols in their composition, and consequently higher membrane fluidity, than RPMI-grown cells. GC-MS analysis demonstrated a remodulation in the sterol profile in SCFM- compared to RPMI-grown cells. Accordingly, when the MIC assay was performed in the presence of the membrane stressor NaCl (3%), the susceptibility to voriconazole and fluconazole increased more in SCFM- than RPMI-grown cells. Conclusions Scedosporium / Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals. [ABSTRACT FROM AUTHOR]

Sphingolipids are vital membrane components in in mammalian cells, plants, and various microbes. We aimed to explore and exploit the sphingolipid biosynthesis pathways in an oleaginous and dimorphic yeast Yarrowia lipolytica by constructing and characterizing mutant strains with specific gene deletions and integrating exogenous genes to enhance the production of long-chain bases (LCBs) and glucosylceramides (GlcCers). To block the fungal/plant-specific phytosphingosine (PHS) pathway, we deleted the SUR2 gene encoding a sphinganine C4-hydroxylase, resulting in a remarkably elevated secretory production of dihydrosphingosine (DHS) and sphingosine (So) without acetylation. The Y. lipolytica SUR2 deletion (Ylsur2 Δ) strain displayed retarded growth, increased pseudohyphal formation and stress sensitivity, along with the altered profiles of inositolphosphate-containing ceramides, GlcCers, and sterols. The subsequent disruption of the SLD1 gene, encoding a fungal/plant-specific Δ8 sphingolipid desaturase, restored filamentous growth in the Ylsur2 Δ strain to a yeast-type form and further increased the production of human-type GlcCers. Additional introduction of mouse alkaline ceramidase 1 (maCER1) into the Ylsur2 Δ sld1 Δ double mutants considerably increased DHS and So production while decreasing GlcCers. The production yields of LCBs from the Ylsur2 Δ sld1 Δ/ maCER1 strain increased in proportion to the C/N ratio in the N-source optimized medium, leading to production of 1.4 g/L non-acetylated DHS at the 5 L fed-batch fermentation with glucose feeding. This study highlights the feasibility of using the engineered Y. lipolytica strains as a cell factory for valuable sphingolipid derivatives for pharmaceuticals, cosmeceuticals, and nutraceuticals. [Display omitted] • Yarrowia lipolytica was engineered for production of sphingolipid derivatives. • SUR2 deletion enhanced secretory production of sphingoid bases without acetylation. • Subsequent SLD1 deletion recovered yeast-type growth and boosted human-type GlcCers. • Mouse alkaline ceramidase 1 expression increased the production of DHS and sphingosine. • Fed-batch fermentation with glucose feeding produced 1.4 g/L non-acetylated DHS. [ABSTRACT FROM AUTHOR]

Mushrooms are a raw material rich in many nutritional compounds, and that is why a number of them are widely known as functional food. They contain fatty acids, carbohydrates, lycopene, sterols, lovastatin, trace elements, and other valuable compounds that show a wide range of properties, such as hepatoprotective, anticancer, antiviral, etc. For more efficient utilisation of mushrooms' biologically active substances, widespread supercritical carbon dioxide extraction (Sc-CO2) was used as an efficient way to isolate the high-value phytoconstituents from this type of raw material. Using Sc-CO2, the extracts of five types of edible mushrooms—Lycoperdon saccatum, Pleurotus ostreatus, Craterellus cornucopioides, Russula Cyanoxantha and Cantharellus cibarius—were obtained. During the Sc-CO2 process, the extraction time was reduced to 4 h compared to the prolonged process time applied in the typical traditional techniques (6–24 h). The extraction pressure (30 MPa) and temperature (40 °C) were constant. Fatty acids and the compounds of steroid structures were determined in the obtained extracts using GC–MS and GC–FID methods of analysis. The dominant compounds identified in the lipid extracts were fatty acids (linoleic, oleic, palmitic and stearic) and sterols (ergosterol, 7,22-ergostadienone and 7,22-ergostadienol). For complete insight into the process and to obtain the value of the extracts, chemometric analysis is provided. Principal component analysis (PCA) and hierarchical cluster analysis (HCA), as well as k-means clustering, showed that Craterellus cornucopioides was distinguished based on the extraction yield results. [ABSTRACT FROM AUTHOR]

EH (Euphorbia Humifusa) is commonly known as ground spurge, contains various compounds such as flavonoids, triterpenes, coumarins, sterols, tannins, and phenolic acids. It exerts a wide spectrum of properties including anti-bacterial, anti-inflammatory, Antioxidant, anti-viral, hypoglycemic, and anti-tumor. In this article, we focus on the antitumor effects of EH and its active constituents, providing evidence for further research on this medicinal herb. [ABSTRACT FROM AUTHOR]

Objectives Ganoderma lucidum (GL) is a white rot fungus widely used for its pharmacological properties and health benefits. GL consists of several biological components, including polysaccharides, sterols, and triterpenoids. Triterpenoids are often found in GL in the form of lanostane-type triterpenoids with quadrilateral carbon structures. Key findings The study revealed that triterpenoids have diverse biological properties and can be categorized based on their functional groups. Triterpenoids derived from GL have shown potential medicinal applications. They can disrupt the cell cycle by inhibiting β-catenin or protein kinase C activity, leading to anti-cancer, anti-inflammatory, and anti-diabetic effects. They can also reduce the production of inflammatory cytokines, thus mitigating inflammation. Additionally, triterpenoids have been found to enhance the immune system's defenses against various health conditions. They possess antioxidant, antiparasitic, anti-hyperlipidemic, and antimicrobial activities, making them suitable for pharmaceutical applications. Furthermore, triterpenoids are believed to afford radioprotection to DNA, protecting it from radiation damage. Summary This review focuses on the types of triterpenoids isolated from GL, their synthesis pathways, and their chemical structures. Additionally, it highlights the pharmacological characteristics of triterpenoids derived from GL, emphasizing their significant role in various therapeutic applications and health benefits for both humans and animals. [ABSTRACT FROM AUTHOR]

Herbal medications are essential for treating a variety of liver disorders; the majority of them accelerate the liver's natural healing process. Both the Indian traditional medical system and ethnomedical practices use a variety of medicinal plants and their preparations to treat liver diseases. Coarsely ground shade-dried plant materials chosen for their hepatoprotective properties were extracted using several solvent systems in the current investigation. Following concentration, the extracts undergo first physical and phytochemical analysis to determine the type of active ingredients present and to evaluate the quality of the plant material. Numerous phytoconstituents, including glycosides, carbohydrates, proteins, amino acids, sterols, triterpenes, total phenolic compound, flavonoids, and saponin, were found in the results of the phytochemical analysis. [ABSTRACT FROM AUTHOR]

The variations of the content of the main classes of lipids in the vacuolar membrane under oxidative stress have been investigated. The data obtained suggest the possibility of promoting the autophagy process. During autophagy, membrane contact sites, which are raft structures, have been established between tonoplast and autophagosomes. The results showed a significant increase in the content of raft-forming lipids (sterols, sphingolipids and lipids enriched with saturated fatty acids), what induce an elevation the number of membrane contact sites and activation of such a protective mechanism as autophagy under oxidative stress. [ABSTRACT FROM AUTHOR]

This study investigates the performance of cyclopentyl methyl ether (CPME) in the extraction of fenugreek seed oil, aiming to replace the conventionally used hexane. The efficiency of this alternative solvent was evaluated first through in silico methods (based on Hansen Solubility Parameters (HSPs) and Conductor-like Screening Model for Real Solvent (COSMO-RS) simulations), followed by experimental studies. Solubility computational predictions analysis revealed that CPME exhibits superior solvation power compared to hexane. Experimentally, CPME demonstrated a significantly higher oil yield (7.23%) compared to hexane (4.25%) and a better retention of beneficial unsaturated fatty acids than hexane. Additionally, the physicochemical properties of oils extracted with CPME showed enhanced oxidative stability, sterol, tocopherol, and phenolic contents, leading to superior antioxidant and antibacterial activities. Importantly, CPME's low volatile organic compound (VOC) emissions further establish it as a more sustainable and environmentally friendly alternative to hexane, aligning with contemporary goals of reducing harmful emissions in extraction processes. Thus, this paper highlights the functional advantages of CPME, focusing on its efficiency, selectivity, and enhanced retention of bioactive compounds, positioning it as a superior extraction solvent for fenugreek seed oil compared to hexane. [ABSTRACT FROM AUTHOR]

Steranes preserved in sedimentary rocks serve as molecular fossils, which are thought to record the expansion of eukaryote life through the Neoproterozoic Era ( ~ 1000-541 Ma). Scientists hypothesize that ancient C27 steranes originated from cholesterol, the major sterol produced by living red algae and animals. Similarly, C28 and C29 steranes are thought to be derived from the sterols of prehistoric fungi, green algae, and other microbial eukaryotes. However, recent work on annelid worms-an advanced group of eumetazoan animals-shows that they are also capable of producing C28 and C29 sterols. In this paper, we explore the evolutionary history of the 24-C sterol methyltransferase (smt) gene in animals, which is required to make C28+ sterols. We find evidence that the smt gene was vertically inherited through animals, suggesting early eumetazoans were capable of C28+ sterol synthesis. Our molecular clock of the animal smt gene demonstrates that its diversification coincides with the rise of C28 and C29 steranes in the Neoproterozoic. This study supports the hypothesis that early eumetazoans were capable of making C28+ sterols and that many animal lineages independently abandoned its biosynthesis around the end-Neoproterozoic, coinciding with the rise of abundant eukaryotic prey.

Plant sterols encompass phytosterols and phytostanols, with over 250 identified types. They've garnered attention in the food industry due to their potential hypocholesterolemic effects. This manuscript offers a current view phytosterols content in foods, their bioaccessibility, bioavailability, and metabolic benefits based on existing preclinical and clinical data. Published articles from 2016 to 2023 regarding the effect of sitosterol, sitostanol, campesterol, campestanol, stigmasterol, and mixed phytosterols on preclinical models and clinical trials were included. Food and technology-related issues were also discussed. Phytosterols's bioavailability in food is limited, exhibiting vulnerability to oxidation, low water solubility, and a distinctive taste. Nevertheless, various technological approaches have been devised to enhance its inclusion in food, ensuring adequate doses for harnessing its cholesterol-lowering potential. This effect has been extensively researched, alongside its hypoglycemic and anti-inflammatory properties. There's a need to create novel functional foods enriched with phytosterols to attain the daily dosage required to leverage its hypercholesterolemic, hypoglycemic, anti-inflammatory, and other ongoing beneficial effects. [ABSTRACT FROM AUTHOR]

Chocolate, particularly dark chocolate, is recognized for its antioxidant properties attributed to the presence of flavonoids that promote cardiovascular health. Enriching chocolate with phytosterols, naturally occurring plant compounds known to be effective in reducing cholesterol levels, has the potential to enhance cardiovascular benefits. The incorporation of phytosterols into chocolate provides a palatable and cost-effective means of delivering these beneficial compounds to the body. This study examined the concentrations of sterols and stanols, as well as the antioxidant properties of dark chocolate enriched with plant-derived sterols and stanols. A commercially available preparation containing phytosterol esters (Vegapure® 95 WE) was utilized for this enrichment. Four levels of phytosterol esters (3, 6, 9, and 12%) were added at two distinct stages of chocolate processing: conching and tempering. Sterol and stanol contents were analyzed chromatographically, total phenolic content was determined using the Folin–Ciocalteu method, and antioxidant capacity was assessed via the DPPH assay. Additionally, a sensory evaluation was performed to assess the palatability of the enriched chocolates. The enriched chocolates showed significantly increased levels of sitosterol (up to 1117.68 mg/100 g), campesterol (up to 119.10 mg/100 g), and sitostanol (up to 76.42 mg/100 g). The antioxidant capacity of the enriched dark chocolates was more strongly correlated with phenolic compound content than with phytosterol content. Sensory differences, particularly in taste, were also noted, influenced by the addition of phytosterols. The stage at which phytosterol esters were introduced affected the chocolate's properties, with the tempering stage proving to be the more advantageous step for incorporating phytosterols, resulting in a lower loss of bioactive compounds. These findings suggest that enriching dark chocolate with phytosterols improves its nutritional profile and functional properties, positioning it as a potential dietary supplement for cholesterol management and cardiovascular health. [ABSTRACT FROM AUTHOR]

Perenniporia fraxinea is a type of wild macrofungus that is widely distributed globally. This study aimed to explore and understand its medicinal value and potential as a functional food by evaluating the effects of its active ingredients. Specifically, we assessed their hypoglycemic, hypolipidemic, hypouricemic, and anti-nitrite properties. The highest concentrations of flavonoids, polyphenols, triterpenes, and sterols were found in the ethyl acetate extract of the fruiting body, followed by the n-butanol extract. The petroleum ether extract of the mycelium exhibited higher hypoglycemic activity than that of the fruiting body. The water extract of the fruiting body showed the highest ability to lower uric acid, while the petroleum ether extract exhibited the lowest. Lipid-lowering effects were stronger in all extracts except the water extract of the mycelium compared to those of the fruiting body. Additionally, the anti-nitrite activity of the water extract of the mycelium was higher than that of the fruiting body, whereas it was lower in all other extracts. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are specialized organelles that store neutral lipids to reduce the negative effects of lipotoxicity on cells. However, many neutral lipids are precursors for the synthesis of sterols and complex terpenoids, and this sequestration often greatly limits the efficient biosynthesis of sterols and complex terpenoids. In this study, taking 7-dehydrocholesterol (7-DHC) synthesis in Saccharomyces cerevisiae as an example, we revealed the blocking mechanism of LD sequestration on the efficient synthesis of metabolic products and found that LDs can sequester a significant amount of squalene, the precursor of 7-DHC, effectively preventing it from being directed toward the post-squalene pathway. Based on this, a post-squalene pathway was reconstructed on LDs, which resulted in a 28.7% increase in the 7-DHC titer, reaching 684.1 mg/L, whereas the squalene titer was reduced by approximately 97%. Subsequently, the triacylglycerol degradation pathway was weakened to release the storage space in LDs, and the esterification pathway was concurrently strengthened to guide 7-DHC storage within LDs, which further increased 7-DHC production, reaching 792.9 mg/L. Finally, by reducing the NADH/NAD + ratio to alleviate the redox imbalance, the 7-DHC titer reached 867.6 mg/L in shake flask and 5.1 g/L in a 3-L bioreactor, which is the highest reported titer to date. In summary, this study provides new insights into the important role of LDs in sterol synthesis and offers a novel strategy for constructing cell factories for the efficient synthesis of sterol compounds. • Post-squalene module was reconstituted in LDs to enhance 7-DHC synthesis. • 7-DHC productivity was improved by enhancing storage and esterification reaction. • Reducing the NADH/NAD + ratio was beneficial for 7-DHC synthesis. • 7-DHC titer in a 3-L bioreactor reached 5.1 g/L, the highest titer reported to date. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the potential effects between various human plasma lipidomes and endometrioid endometrial cancer (EEC) by using Mendelian randomization (MR) methods. Methods: This study designated a total of 179 human plasma lipidomes from the genome-wide association study (GWAS) database as the exposure variable. An EEC-related dataset from the GWAS (GCST006465) served as the outcome variable. MR analyses used the inverse variance-weighted method (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods for regression calculations, accounting for possible biases induced by linkage disequilibrium and weak instrument variables. Any lipidomes failing to pass heterogeneity and horizontal pleiotropy tests were deemed to lack significant causal impact on the outcome. Results: The results of IVW analysis disclosed that a variety of human plasma lipidomes (n = 15) exhibited a significant causal effect on EEC (p < 0.05). A subset of these lipidomes (n = 13) passed heterogeneity and horizontal pleiotropy tests, which demonstrated consistent and viable causal effects (p < 0.05) including glycerophospholipids, glycerolipids, and sterols. Specifically, phosphatidylcholine (odds ratio [OR]: 1.065-1.129, p < 0.05) exhibited a significant positive causal effect on the occurrence of EEC. Conversely, sterol ester (OR = 0.936, p = 0.007), diacylglycerol (OR = 0.914, p = 0.036), phosphatidylcholine (OR: 0.903-0.927, p < 0.05), phosphatidylethanolamine (OR = 0.907, p = 0.046) and triacylglycerol (OR: 0.880-0.924, p < 0.05) showed a notable negative causal association with EEC, suggesting their inhibitory effects on the EEC occurrence. Conclusions: The study revealed that human plasma lipidomes have complex impacts on EEC through Mendelian randomization. This indicated that the diversity of structural changes in lipidomes could show different effects on subtypes and then affect EEC occurrence. Although these lipids had the potential to be promising biomarkers, they needed to be further clinically validated nevertheless. [ABSTRACT FROM AUTHOR]

Skeletal isomerization of ergosterol peroxide, a primary oxidation product of ergosterol, was investigated under thermal and iron(II)‐mediated conditions. Thermal isomerization resulted in not only the isolation of the predicted 7‐hydroxy‐5,6‐epoxides but also the discovery of the unprecedented 7/9/5‐ring‐fused ergostane for the first time. The iron(II)‐mediated isomerization proceeded at ambient temperature, resulting in the formation of the expected 5,6‐epoxysterols and a ring‐opened bicyclic diketone. The diketone was further converted into novel ergostane under thermal conditions and into (+)‐sarocladione under acidic conditions. All transformations from ergosterol to sarocladione, including the isolation of the unstable diketone intermediate, were achieved at ambient temperature, confirming the biosynthetic pathway of sarocladione. Several mushroom ingredients with a 5,6‐epoxy group were synthesized stereoselectively from the isomerization products, leading to the confirmation or revision of the structures of natural products. The β‐amyloid aggregation inhibitory activity of synthetic sterols was evaluated for the first time to gain insights into the potential for dementia prevention. This study is valuable both for supplying rare sterols found in mushrooms for biological studies and for shedding light on the oxidative metabolic pathways of ergosterol. [ABSTRACT FROM AUTHOR]

Omphalia lapidescens is a macrofungus that is used in traditional Chinese medicine for its insecticidal and stagnation-relieving properties. The active ingredients of this fungus including proteins, polysaccharides and sterols have been demonstrated to exhibit antiparasitic, anti-inflammatory, and antitumor effects. Omphalia has been used in clinical cancer treatment. Many studies on Omphalia have concentrated on its cytotoxicity and anticancer effects. However, the investigation of its natural metabolites remains a significant area for further research. This review presents a comprehensive analysis of the research progress concerning the pharmacological components of Omphalia. The aim of this discussion is to provide a reference for further in-depth study of Omphalia, with the objective of exploring its potential value. Therefore, the focus of this review was on the classification of metabolites in Omphalia and their mechanisms of action. [ABSTRACT FROM AUTHOR]

Currently, due to the increasing impact of anthropogenic factors and changes in solar activity, the temperature on Earth is rising, posing a threat to biodiversity. Lichens are among the most sensitive organisms to climate change. Elevated ambient temperatures can have a significant impact on lichens, resulting in more frequent and intense drying events that can impede metabolic activity. It has been suggested that the possession of a diverse sterol composition may contribute to the tolerance of lichens to adverse temperatures and other biotic and abiotic stresses. The major sterol found in lichens is ergosterol (ERG); however, the regulation of the ERG biosynthetic pathway, specifically the step of epoxidation of squalene to 2,3-oxidosqualene catalyzed by squalene epoxidase during stress, has not been extensively studied. In this study, we used lichen Lobaria pulmonaria as a model species that is well known to be sensitive to air pollution and habitat loss. Using in silico analysis, we identified cDNAs encoding squalene epoxidase from L. pulmonaria, designating them as LpSQE1 for the mycobiont and SrSQE1 for the photobiont Symbiochloris reticulata. Our results showed that compared with a control kept at room temperature (+20 °C), mild temperatures (+4 °C and +30 °C) did not affect the physiology of L. pulmonaria, assessed by changes in membrane integrity, respiration rates, and PSII activity. An extreme negative temperature (−20 °C) noticeably inhibited respiration but did not affect membrane stability. In contrast, treating lichen with a high positive temperature (+40 °C) significantly reduced all physiological parameters. Quantitative PCR analysis revealed that exposing thalli to −20 °C, +4 °C, +30 °C, and +40 °C stimulated the expression levels of LpSQE1 and SrSQE1 and led to a significant upregulation of Hsps. These data provide new information regarding the roles of sterols and Hsps in the response of lichens to climate change. [ABSTRACT FROM AUTHOR]

This study analyzed the physicochemical characteristics, microbial quality, and antioxidant activities of extracts from Parkia biglobosa trunk bark powders collected in four sites (Gonse, Yako, Bobo, and Nobere) in Burkina Faso. The physicochemical characteristics of the extracts and the microbial quality were studied according to European Pharmacopoeia methods. The antioxidant activity of the extracts was also evaluated. The extraction yields varied from 13.82 for the Nobere site to 17.38 for the Gonse site. The study of phytochemical parameters shows that the extracts from the 4 sites had uniform macroscopic characteristics and pH, and they all had a residual moisture content of less than 10%. As for the microbial analysis, the extracts from the trunk bark of the 4 sites all comply with the specifications of the European Pharmacopoeia. Tannins, flavonoids, coumarins, saponins, triterpenes, and sterols were highlighted in all the extracts. The Bobo and Yako sites statistically had the highest total phenolic contents (558.06±19.69 and 532.40±23.78 EAT/g) and tannins (415.58±15.17 and 408.38±25.54 EAT/g). On the other hand, the 4 extracts had the same contents for flavonoids. Concerning the antioxidant activity, all the extracts from the 4 sites had IC50s lower than 4 µg/ml by the ABTS method, and the extracts from the Bobo, Gonse, and Yako sites had IC50 of 6 µg/ml lower than that of the Nobere site. This study made it possible to choose, through the characterization, quantification, and activity of extracts from harvest sites suitable for the pharmaceutical production of phytomedicines. [ABSTRACT FROM AUTHOR]

Moringa trees are found in many parts of the world, including tropical regions, and is a valuable plant for obtaining oil for food and non-food applications. This study aimed to investigate the physicochemical characteristics of oils extracted from moringa seeds. The results showed that Moringa oleifera oil had a refractive index of 1.4781 (at 25ºC), a density of 0.817 g/cm³, and a viscosity of 33.5 mPa/s. In contrast, M. stenopetala oil had a refractive index of 1.4678, a density of 0.820 g/cm³, and a viscosity of 32.0 mPa/s. The chemical characteristics of M. oleifera oil, such as acid value, peroxide value, iodine value, and saponification value, were 0.92, 1.71, 67.07, and 180.00, respectively. For M. stenopetala oil, these values were 0.99, 0.86, 54.40, and 209.00; respectively. Gasliquid chromatography (GLC) was used to detect the fatty acids in the oils, revealing that oleic acid was predominant, followed by palmitic acid. Sterols such as beta-sitosterol and campesterol were also estimated in the moringa oils. Furthermore, the oils demonstrated good oxidative stability [ABSTRACT FROM AUTHOR]

3-ketosteroid-9α-hydroxylase (KSH), a two-component monooxygenase consisting of a Rieske oxygenase KshA and a ferredoxin reductase KshB, is a crucial enzyme involved in C-9 hydroxylation and is indispensable in the microbial catabolism of sterols. However, the in vivo function of KshB remains unclear. In this study, two reductase subunits, KshB1 and KshB2 from Mycobacterium fortuitum ATCC 35855, were first characterized and then engineered in the strain MFΔ kstD , which produces 9-OHAD (9α-hydroxy-4-androstene-3,17-dione), to construct the strains producing AD (4-androstene-3,17-dione). The transcriptional level and specific enzyme activity of KshB1 under phytosterols induction was significantly higher compared to KshB2. After knocking out kshB1 , AD peaked at 1.77 g/L at 48 h, subsequently being fully converted to 9-OHAD. Furthermore, we developed the stable AD-producer MFΔ kstD Δ kshB by null mutation both kshB1 and kshB2 , although no AD was detected by single knocking out kshB2. Through gene complementation and the bioconversion of phytosterols, KshB1 emerged as the primary reductase in the KSH system, with KshB2 serving a complementary role. The stable AD-producer MFΔ kstD Δ kshB could produce 5.18 g/L, 6.91 g/L, and 9.03 g/L AD from the transformation of 10 g/L, 15 g/L, and 20 g/L phytosterols, respectively. In conclusion, these findings highlight a new strategy for the metabolic engineering of Mycobacterium fortuitum , involving the inactivation of the reductase KshB to facilitate the production of C9 non-hydroxylated steroidal intermediates. [Display omitted] • Two reductases, KshB1 and KshB2, were identified in Mycobacterium fortuitum. • KshB1 functions as the primary reductase in the KSH system. • The KshBs were inactivated to construct a strain producing AD (4-androstene-3,17-dione). • The AD-producer yielded 5.18 g/L, 6.91 g/L, and 9.03 g/L AD from 10 g/L, 15 g/L, and 20 g/L phytosterols, respectively. [ABSTRACT FROM AUTHOR]

This study investigated the antiobesity effects of black ginger extract (BGE) in high-fat diet (HFD)-induced obese mice. Mice were divided into six groups: normal diet control (NC, AIN-93G normal diet), 60% HFD control (HFD), HFD containing metformin at 250 mg/kg b.w. (Met, positive control), and HFD containing BGE at 5, 10, or 20 mg/kg b.w. for 15 weeks. BGE administration significantly prevented HFD-induced increases in weight gain, organ weight, and adipose tissue mass. Furthermore, it resulted in decreased adipogenesis and lipogenesis-related factors, including phosphorylated mitogen-activated protein kinase, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins, sterol regulatory element-binding protein 1, phosphorylated cAMP response element-binding protein, glucose-6-phosphate dehydrogenase, fatty acid synthase, dephosphorylated ATP-citrate lyase, dephosphorylated acetyl-CoA carboxylase, and lipoprotein lipase, in white adipose tissues. Moreover, BGE administration enhanced lipolysis in white adipose tissue, as evidenced by elevated levels of adipose triglyceride lipase, phosphorylated hormone-sensitive lipase, and protein kinase A, along with reduced levels of perilipin and phosphodiesterase 3B. BGE induced thermogenesis in brown adipose tissues, as reflected by the increased expression of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1 and decreased levels of fatty acid-binding protein 4. In conclusion, this study provides comprehensive evidence supporting the antiobesity effects of BGE, elucidating the underlying molecular mechanisms involved in preventing weight gain, suppressing adipogenesis, promoting lipolysis, and stimulating thermogenesis. These findings suggest the potential therapeutic utility of BGE in combating obesity and associated metabolic disorders (KHGASP-2023-034). [ABSTRACT FROM AUTHOR]

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Despite longstanding excitement and progress toward understanding liquid-liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid-liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling because only two components are required for liquid-liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol-lipid. By evaluating a panel of sterol-lipids, some of which are present in bacteria, we found a minimal bilayer of only two components (PChemsPC and diPhyPC) that robustly demixes into micron-scale, liquid phases. It suggests an additional role for sterol-lipids in nature, and it reveals a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are straightforward to determine and will be consistent across multiple laboratories. [ABSTRACT FROM AUTHOR]

Ganoderma, a traditional medicine in Asian countries, has been used to prevent and treat various ailments for centuries. Ganoderma neo-japonicum (synonym Ganoderma bambusicola), also known as purple Lingzhi, is a species that is currently underutilised when compared to Ganoderma lucidum (Lingzhi). However, in recent decades, this mushroom has garnered significant attention due to its ethnomedicinal uses, especially in Southeast Asia regions like Malaysia. The taxonomy and nomenclature of this mushroom have been extensively studied. Numerous publications have reported that G. neo-japonicum displays a variety of medicinal properties, including antioxidation, anticancer, anti-hyperglycaemic, genoprotective, hepatoprotective, neuritogenic, and antidiabetic effects, both in vitro and in vivo. With the surge of research findings on this mushroom, this review aims to provide a systematic bibliometric analysis of G. neo-japonicum, published between 1991 to 2021. Additionally, the taxonomic description of this mushroom is discussed in detail. Our review reveals that G. neo-japonicum contains polysaccharides (α/β-D-glucans), triterpenoids, and sterols/ergosterol. However, the existing literature suggests that these active compounds have not yet been explored to their full potential as drug candidates. Moreover, most of the studies are preclinical and have several drawbacks. In conclusion, G. neo-japonicum possesses valuable pharmacological activities that merit further exploration. [ABSTRACT FROM AUTHOR]

Objectives: The genus Glochidion (the family Phyllanthaceae) is used for various medicinal purposes, such as dysentery, diarrhea, cough, and skin protection. A review of phytochemical and pharmacological aspects for this remains unavailable. The current study tends to sum up a detailed list of phytochemicals, and their role in biological examinations. Methods: References in English were obtained by an extensive search across various electronic data sources, encompassing Web of Science, PubMed, Google Scholar, and Science Direct. The "Sci-Finder" was also utilized to find references and revise chemical structures. Referenced documents have been gathered from the 1960s to date. It also noted that Glochidion, phytochemistry, and pharmacology are likely the keywords to seek for references. Results: Over 240 naturally occurring phytochemicals were isolated and identified from various Glochidion tissues, including terpenoids, sterols, saponins, lignans, flavonoids, mono -phenols, megastigmanes, butenolides, glycosides, alkaloids, cyanogens, tocopherols, fatty acids, and others. Three naturally occurring triterpenoids glochidonol, glochidiol, and glochidone are the likely characteristic metabolites, being isolated frequently. Glochidion crude extracts and their isolated compounds have been demonstrated as potential agents in various pharmacological targets, such as cytotoxicity, antioxidant, antiinflammation, and neuron and liver protection. Conclusion: Several isolates acted as promising agents in pharmacological assays. The anticancer mechanisms of various triterpenoids and saponins, especially new and potential compounds, are expected. Pharmacological advancements to enhance the efficacies of Glochidion constituents, such as synergistic combinations and nano-drug formulations, are encouraged. [ABSTRACT FROM AUTHOR]

Botanical varieties of hemp differ in chemical composition, plant morphology, agronomy, and industrial suitability. Hemp is popular for cultivation for the production of cannabinoid oil, fiber production, biomass, etc. The fertilization process is one of the most important factors affecting the plant, both its condition and chemical composition. So far, research has been carried out proving that hemp is a valuable source of, among others: fatty acids, amino acids, acids, vitamins, numerous micro- and macroelements, and antioxidant compounds. In this experiment, it was decided to check the possibility of harvesting hemp panicles twice in one year. The purpose of this treatment is to use one plant to produce cannabidiol oil and grain. The main aim of the research was to determine bioactive compounds in hemp seeds and to determine whether the cultivation method affects their content and quantity. Based on the research conducted, it was observed that hemp can be grown in two directions at the same time and harvested twice because its health-promoting properties do not lose their value. It was found that regardless of whether hemp is grown solely for seeds or to obtain essential oils and then seeds, the type of fertilization does not affect the content of phenolic acids (e.g., syringic acid: 69.69–75.14 μg/100 g, vanillic acid: 1.47–1.63 μg/100 g). Based on the conducted research, it was found that essential oils can be obtained from one plant in the summer and seeds from Henola hemp cultivation in the autumn, because such a treatment does not affect the content of the discussed compounds. [ABSTRACT FROM AUTHOR]

Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1β, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS. [ABSTRACT FROM AUTHOR]

Background: Seaweeds are macroalgae containing bioactive compounds that have positively impacted the biomedical field due to polysaccharides, sterols and glycolipids, showing a diverse range of pharmacological and biological properties. Eating a diet high in marine items will lessen the risk of developing diabetes, cancer and obesity. Purpose: The exploration of medically useful seaweeds is required to identify drugs and drug targets and reduce the risk of developing diseases. Methodology: The PubMed search was done with the MESH terms such as seaweed and Marine algae pharmacological activity results were obtained as 748 results. We filtered out the articles and entered key terms related to our area of interest to find the results. The seaweed species in India are listed with Tamil Nadu contributing the most and Orissa the least. The type of algae is also mentioned. Results: Marine algae have been employed in industry and medicine as a novel food with possible nutritional benefits. Furthermore, it has been demonstrated that marine algae are a rich source of naturally occurring bioactive substances with activities such as anti-diabetic, hepatoprotective, antiviral, antifungal, antibacterial, antimicrobial, antioxidant, anti-inflammatory, anti-hypercholesterolemia and hypolipidemia. Conclusion: The current review focuses on the bioactivities and potential pharmaceutical activity of marine algae discovered in India. The present review article showed that there are many seaweeds of medical importance, and it is necessary to explore them to minimize disease progression and prolong the individual's survival. [ABSTRACT FROM AUTHOR]

Water deficit and heat are the primary abiotic stresses affecting plants. We conducted in vitro experiments to investigate how citron watermelon seedlings respond to water deficit and heat, focusing on growth, water status, reserve mobilization, hydrolase activity, and metabolite partitioning, including non-structural carbohydrate availability, during the vulnerable stage of seedling establishment crucial for crop production. To reveal the involvement of phytosterols (stigmasterol, sitosterol, and campesterol) in combined stress tolerance, four citron watermelon genotypes were investigated under varying osmotic potential [−0.05 MPa, −0.09 MPa and −0.19 MPa] and temperature (26 °C and 38 °C). Phytosterols were analyzed by gas chromatography–mass spectrometry (GC–MS). Seedlings subjected to osmotic stress from polyethylene glycol (PEG) exhibited reduced growth, linked to relative water content (RWC) changes, delayed starch mobilization in cotyle-dons, and decreased non-structural carbohydrate availability in roots. High temperature retarded the photosynthetic apparatus's establishment and compromised photosynthetic pigment activity and dry matter production. The results suggest that inherent stress tolerance in citron watermelon is characterized by the increased accumulation of lipids, mainly sterols, especially in heat/drought-stressed plants. This study provides valuable information about the metabolic response of citron watermelon to combined stress and metabolites identified, which will encourage further study in transcriptome and proteomics to improve drought tolerance. [ABSTRACT FROM AUTHOR]

Olive growing is undergoing a transition from traditional cultivation systems to a more technological model characterized by increased mechanization and a higher density of plants per hectare. This shift implies the use of less vigorous varieties that can adapt to the new system. Most traditional varieties are highly vigorous, and breeding programs can provide solutions to this challenge. This study investigates the parental effect on different agronomic and olive oil characteristics and its role in breeding programs. The objectives were to evaluate and characterize different agronomic and olive oil traits in the progenies from 'Arbosana' × 'Sikitita' cross and its reciprocal cross 'Sikitita' × 'Arbosana'. The results showed a high variability of the characters evaluated in the progenitors of the reciprocal crosses. The highest coefficients of variation were observed in traits related to ripening index, phenolic compounds, polyunsaturated fatty acids, and Δ5-avenasterol, with phenolic content exhibiting the greatest variability. No statistically significant maternal effect was detected for any of the evaluated traits, although a slight positive maternal effect was systematically observed in the mean values of the evaluated traits. These results suggest that the maternal effect on olive is quite subtle, although due to a slight tendency of the maternal effect in the descriptive analyses, future studies are suggested to understand in depth the possible maternal effect on olive breeding. [ABSTRACT FROM AUTHOR]