Search

BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.

Squalene (SQ) is a well-known antioxidant and anti-inflammatory agent that provides promising anti-aging and UV-protective roles on human skin. However, its strong hydrophobic nature, accompanied by issues such as poor solubility and limited tissue permeation, has created challenges for scientists to investigate its untapped potential in more complex conditions, including cancer progression. The present study assessed the potent anti-metastatic properties of a newly synthesized amphiphilic ethylene glycol SQ derivative (SQ-diEG) in melanoma, the most fatal skin cancer. In vitro and in vivo experiments have discovered that SQ-diEG may exert its potential on melanoma malignancy through the mitochondria-mediated caspase activation apoptotic signaling pathway. The potent anti-metastatic effect of SQ-diEG was observed in vitro using highly proliferative and aggressive melanoma cells. Administration of SQ-diEG (25 mg/kg) significantly decreased the tumor burden on the lung and inhibited the metastasis-associated proteins and gene markers in B16F10 lung colonization mice model. Furthermore, global gene profiling also revealed a promising role of SQ-diEG in tumor microenvironment. We anticipated that the amphiphilic nature of the SQ compound bearing ethylene glycol oligomers could potentially augment its ability to reach the pathology site, thus enhancing its therapeutic potential in melanoma. [ABSTRACT FROM AUTHOR]

China is a major producer and consumer of vegetable oils, and the processing of oilseeds generates a large amount of by-products such as vegetable oil deodorizer distillate, soapstock, and acid oil. These by-products are rich in active substances like phytosterols, natural vitamin E, and squalene, which have biological functions such as regulating cholesterol metabolism, antibacterial, antiinflammatory, and antioxidant properties, as well as promoting animal growth and improving the quality of animal products. Therefore, extracting natural active substances from vegetable oil processing byproducts and conducting research and application on their utilization as feed resources can help address many challenges currently faced by the feed development and livestock industry. This paper focuses on the latest research reports on phytosterols, natural vitamin E, and squalene in vegetable oils used in livestock and poultry production, analyzing their application effects and mechanisms of action, with the aim of providing theoretical basis and practical guidance for healthy animal farming. [ABSTRACT FROM AUTHOR]

This study explores the potential of a nanomedicine approach, using Leu-enkephalin-squalene nanoparticles (LENK-SQ NPs) for managing long-lasting pain. It was observed that the nanomedicine significantly improved the pharmacological efficacy of the Leu-enkephalin, a fast metabolized neuropeptide, in a rat model of acute inflammatory pain, providing local analgesic effect, while minimizing potential systemic side effects by circumventing central nervous system. The LENK-SQ NPs were tested in a rat model of postoperative pain (Brennan's rodent plantar incision model) using continuous infusion via Alzet® pump, with an additional bolus injection. The analgesic activity was assessed through stimulus-evoked methods, such as the von Frey and Hargreaves tests. Both mechanical and thermal hyperalgesia were significantly reduced at days 2 and 3 post-incision. An additional pharmacokinetic study was conducted, showing that LENK-SQ NPs allowed a sustained circulation of the neuropeptide under its prodrug form. On the other hand, the biodistribution of fluorescently labelled LENK-SQ NPs revealed their selective accumulation in the incised paw within the first hour post administration, followed by a disassembly of the NPs, starting 24 h later. The study proposes the following multi-step mechanism for the anti-nociceptive pharmacological activity of LENK-SQ NPs: (i) protection of the neuropeptide from metabolization into the bloodstream, (ii) targeted accumulation of the nanoparticles within the incised painful tissue and (iii) gradual release of LENK at the onset of the inflammatory process, leading to the observed analgesic activity. [Display omitted] • Continuous L-enkephalin-squalene nanoparticles infusion relieves postoperative pain. • The long-lasting analgesia is obtained via in situ targeting of nanoparticles. • L-enkephalin-squalene nanoparticles increase the plasma half-life of the neuropeptide. • The accumulation of nanoparticles into painful tissues does not require transcytosis. [ABSTRACT FROM AUTHOR]

Main conclusion: This review ascertains amaranth grains as a potent crop for food security and sustainable food systems by highlighting its agricultural advantages, health benefits and applications in the food, packaging, and brewing industry. The global population surge and rapidly transitioning climatic conditions necessitate the maximization of nutritional crop yield to mitigate malnutrition resulting from food and nutrition insecurity. The modern agricultural practices adopted to maximize the yield of the conventional staple crops are heavily contingent on the depleting natural resources and are contributing extensively to the contamination of these natural resources. Furthermore, these agricultural practices are also causing detrimental effects on the environment like rising emission of greenhouse gasses and increased water footprints. To address these challenges while ensuring sustainable nutrient-rich crop production, it is imperative to utilize underutilized crops like Amaranthus. Amaranth grains are gluten-free pseudo-cereals that are gaining much prominence owing to their abundance in vital nutrients and bio-active components, potential health benefits, resilience to adverse climatic and soil conditions, minimum agricultural input requirements, potential of generating income for small holder farmers as well as various applications across the sustainable value chain. However, due to the limited awareness of these potential benefits of the amaranth grains among the consumers, researchers, and policymakers, they have remained untapped. This review paper enunciates the nutritional composition and potential health benefits of the grains while briefly discussing their various applications in food and beverage industries and accentuating the need to explore further possibilities of valorizing amaranth grains to maximize their utilization along the value chain. [ABSTRACT FROM AUTHOR]

ABSTRACT Squalene is a natural triterpenoid and a biosynthetic precursor of steroids and hopanoids in microorganisms, plants, humans, and other animals. Squalene has exceptional properties, such as its antioxidant activity, a high penetrability of the skin, and the ability to trigger the immune system, promoting its application in the cosmetic, sustenance, and pharmaceutical industries. Because sharks are the primary source of squalene, there is a need to identify low‐cost, environment friendly, and sustainable alternatives for producing squalene commercially. This shift has prompted scientists to apply biotechnological advances to research microorganisms for synthesizing squalene. This review summarizes recent metabolic and bioprocess engineering strategies in various microorganisms for the biotechnological production of this valuable molecule. [ABSTRACT FROM AUTHOR]

Dipteryx lacunifera, known as gurguéia nut, is a potential crop for obtaining specialty oils. The processing of gurguéia nut to obtain the oil generates circa 635 g kg−1 of cake, a biomass rich in residual oil. A sequential approach using hydraulic pressing (HP) and supercritical fluid extraction with CO2 (SFE-CO2) has been employed to maximize the oil recovery from gurguéia nut. High contents of β-sitosterol (55.8 mg 100 g−1), stigmasterol (38.6 mg 100 g−1), campesterol (13.9 mg 100 g−1), squalene (668.7 mg 100 g−1), total phenolics (6.1 mg GAE 100 g−1) and antioxidant potential (4.2 mg TE 100 g−1 in FRAP; 5.4% in DPPH; and 54.3% in ILP) were observed in the oil from SFE-CO2 as compared to HP and Soxhlet oils. Significant contents of γ- and α-tocopherol (3.5–4.2, and 18.2–21.5 µg g–1) were found in oils. Oleic (~ 60%), palmitic (9.9–18.9%), and linoleic (11.6–12.9%) were the major fatty acids. As a result, the main triacylglycerols were OOO (23.0–35.5 wt%), POO (13.4–31.3 wt%), and OLO (2.1–15.6 wt%). Thermal analysis revealed two major exothermic events during crystallization and a single peak on melting, also showing that gurguéia oils are liquid at 20 °C. Combining sustainable technologies was useful for valorizing residual biomass from hydraulic pressing to obtaining a high-quality oil with potential uses in the food, cosmetic and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Summary: Building sustainable platforms to produce biofuels and specialty chemicals has become an increasingly important strategy to supplement and replace fossil fuels and petrochemical‐derived products. Terpenoids are the most diverse class of natural products that have many commercial roles as specialty chemicals. Poplar is a fast growing, biomassdense bioenergy crop with many species known to produce large amounts of the hemiterpene isoprene, suggesting an inherent capacity to produce significant quantities of other terpenes. Here we aimed to engineer poplar with optimized pathways to produce squalene, a triterpene commonly used in cosmetic oils, a potential biofuel candidate, and the precursor to the further diversified classes of triterpenoids and sterols. The squalene production pathways were either re‐targeted from the cytosol to plastids or co‐produced with lipid droplets in the cytosol. Squalene and lipid droplet co‐production appeared to be toxic, which we hypothesize to be due to disruption of adventitious root formation, suggesting a need for tissue specific production. Plastidial squalene production enabled up to 0.63 mg/g fresh weight in leaf tissue, which also resulted in reductions in isoprene emission and photosynthesis. These results were also studied through a technoeconomic analysis, providing further insight into developing poplar as a production host. [ABSTRACT FROM AUTHOR]

Background: It is known that tropospheric ozone (O3) generated from pollutants reacting with UV forms lipid peroxidation products and induces oxidative stress to the skin. With the ever‐increasing consumer awareness of the effects pollution has on skin, more testing methods will be needed to evaluate cosmetic ingredients. Recently, others have shown how antioxidants are able to reduce the effects from ozone on skin through in vitro, ex vivo and clinical studies where human subjects place their arms into large stationary chambers. Aims: To develop a small, easy to use ozone exposure module (OEM) that can be used on various sites of the body and to validate this device for use in testing the ability of topical products to mitigate the effects of ozone exposure on the skin. Materials and Methods: We have produced an OEM which can generate levels of ozone in excess of 1000 ppb and can be set to achieve the equivalent exposure to what is found in polluted environmental conditions. After exposure we used D‐squame discs to remove the sebum and analytically quantitate squalene depletion. Squalene, which is very sensitive to ROS, easily oxidizes into early metabolite squalene monohydroperoxide (SQOOH) with ozone exposure. Results: We were able to show decreases in squalene levels after exposure and protective effects from a topical formulation. Conclusion: This generator will be a useful tool for researchers to easily create a small and safe exposure from ozone for clinical testing. [ABSTRACT FROM AUTHOR]

The quality of fried products greatly depends on the changes occurring during frying. The purpose of this work was to study the lipid quality changes taking place in selected frozen foods after domestic deep-frying. Conventional, high-linoleic sunflower oil (HLSO) and high-oleic sunflower oil (HOSO) were used, and the frozen foods selected were French fries, croquettes, and nuggets. The foods were fried in domestic fryers under discontinuous conditions. Analyses included fatty acid composition, sterols, tocopherols, squalene, and lipid alteration levels. In all fried foods, the content of lipids increased after frying, which is consistent with previous findings. However, the lipid exchange between the food and the oil greatly depended on the food characteristics. Specifically, the levels of frying oil in the food lipids were about 90, 40, and 58% for French fries, croquettes, and nuggets, respectively. The main results obtained showed that lipid alteration levels considerably decreased and amounts of sterols and tocopherols significantly increased in French fries' lipids after frying. In both chicken products, croquettes and nuggets, the best quality improvement observed was a significant decrease in cholesterol in food lipids due to the lipid exchange. Overall, frying with HLSO and HOSO improved the quality and nutritional properties of all products tested. [ABSTRACT FROM AUTHOR]

Background: There is a concerning rise in antifungal‐resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. Objectives: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. Methods: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18‐month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real‐time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). Results: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. Conclusion: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk. [ABSTRACT FROM AUTHOR]

All eight theoretical stereoisomers of (10S)‐Ambrox have been synthesized by enzymatic polycyclization of the four geometric isomers of homofarnesol with selected squalene hopene cyclases. This includes the highly strained (+)‐(8S,9S)‐Ambrox, an isomer historically considered unlikely to exist. The enantiomeric (10R)‐series has been prepared by a combination of diastereoselective synthesis and preparative chiral HPLC. Thus, for the first time, the synthesis and sensory properties of all but one stereoisomers of Ambrox are presented. The results solve a long standing peradventure: the commercial product (−)‐Ambrox exhibits by far the strongest odour, the previously described 9‐epi‐Ambrox is 26 times weaker. The enantiomer difference between (−)‐and (+)‐Ambrox was also found much higher than in previous reports (1000 vs. 8 times). The (8R)‐configuration was identified as the single most important structural feature for high odour strength. [ABSTRACT FROM AUTHOR]

Eleven kinds of Camellia oleifera seed oils (CSOs) were evaluated in terms of chemical constituents, antioxidant activities, acid value (AV) as well as peroxide value (POV). These CSOs contained abundant β-sitosterol, squalene, α-tocopherol and phenolics, in which the squalene was the distinct constituent with the content between 45.8±0.8 and 184.1±5.5 mg/kg. The β-sitosterol ranging from 143.7±4.8 to 1704.6±72.0 mg/kg contributed a considerable content to total accompaniments. Palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid were present in these CSOs, in which the dominant fatty acid was oleic acid with the content between 59.66±0.72 and 82.89±2.16 g/100 g. The AV ranged from 0.1±0.0 to 1.3±0.0 mg KOH/g, and the POV was between 0.1±0.0 and 1.0±0.0 g/100 g. These CSOs showed antioxidant activity based on DPPH and ABTS radical scavenging assay. Both α-tocopherol and β-sitosterol contents showed a positive correlation with DPPH and ABTS values, respectively, while the α-tocopherol content showed a negative correlation with AV. These results suggested that CSO can be categorized into high oleic acid vegetable oil with abundant active constituents, of which the quality presented variation among different origins. These accompaniments may contribute to the delay of its quality deterioration. [ABSTRACT FROM AUTHOR]

Silphium integrifolium Michx. (silflower), a perennial plant, is of great interest as a potential new oilseed crop due to its long, strong, deep, extensive root systems, which can prevent erosion, capture dissolved nitrogen, and out‐compete weeds eliminating the need for frequent irrigation and herbicide uses. In this study, oil was extracted from unhulled silflower seeds, and its composition and oxidative stability were evaluated. The oil content in unhulled silflower seeds was 15.2% (wt/wt), and its fatty acid composition was similar to that of sunflower oil. The level of total polar compounds (TPC) in the oil was 12.3% (wt/wt), and the content of total phenolics was 1.12 mg gallic acid equivalent (GAE)/g oil. Noteworthily, 4.89% squalene was isolated from silflower oil indicating its potential application as an alternative source of squalene. Silflower oil had lower oxidative stability as indicated by the oxidative stability index (OSI) at 110°C and thermogravimetric analysis (TGA), presumably due to its high level of chlorophyll (1002.8 mg/kg). Even after a typical refining process involving degumming, alkali refining, and bleaching with Fuller's earth, silflower oil contained 725.5 mg/kg chlorophyll, and its oxidative stability was not improved. Further treatments with bleaching agents including bentonite, sepiolite, and Tonsil® lowered the chlorophyll level to 4.2, 474.5, and 38.5 mg/kg, respectively, and some aspects of oxidative stability were improved and better than those of refined sunflower oil. This study presents the potential of silflower oil as new edible oil and a great plant source of squalene. [ABSTRACT FROM AUTHOR]

The high biological activity of cultivated and wild purslane offers broad possibilities for utilizing this plant in medicine and human nutrition. To assess the prospects of obtaining new functional food products based on the wild form of P. oleracea L., foliar biofortification of this species with sodium selenate (VI) was carried out, and the changes in leaf and seed biochemical characteristics were investigated. Selenium significantly enhanced plant yield, photosynthetic pigments and the ascorbic acid content, and showed a tendency to seed productivity increase. The application of selenium augmented quinic acid content in leaves by 1.7 times but did not affect the oxalic acid content. Oxalic acid prevailed in wild purslane and quinic acid in cultivated purslane (cv. Makovey). Seed oil in Se-enriched purslane was characterized by a two-fold decrease in saturated fatty acids and squalene and 2.3-fold decrease in malonic dialdehyde content, along with a 1.4-fold increase in ascorbic acid. Selenium supplementation resulted in an increase in total lipids and mono- and di-unsaturated fatty acids and did not affect the concentration of ω-3 fatty acids and sterol accumulation. Among the identified sterols, only the minor ones (fucosterol, 7-stigmasterol and ∆7-avenosterol) showed a slight decrease upon Se supply. Compared to seeds of cv. Makovey, wild purslane seeds had higher levels of antioxidant activity by a factor of 2 and of polyphenols by a factor of 3.2 but did not differ significantly in oil fatty acid composition. The results indicate the importance of wild purslane leaves/seeds both fortified and not fortified with Se in human nutrition and medicine. [ABSTRACT FROM AUTHOR]

Abstract Coconut (Cocos nucifera) leaves, an unutilized resource, enriched with valuable bioactive compounds. Spectral analysis of purified pentane fraction of coconut leaves revealed the presence of a squalene analog named 4,4′-diapophytofluene or in short 4,4′-DPE (C30H46). Pure squalene standard (PSQ) showed cytotoxicity after 8 µg/ml concentration whereas 4,4′-DPE exhibited no cytotoxic effects up to 16 µg/ml concentration. On senescence-induced WI38 cells, 4,4′-DPE displayed better percentage of cell viability (164.5% at 24 h, 159.4% at 48 h and 148% at 72 h) compared to PSQ and BSQ (bio-source squalene) with same time duration. Similar trend of result was found in HaCaT cells. SA-β-gal assay showed that number of β-galactosidase positive cells were significantly decreased in senescent cells (WI38 and HaCaT) after treated with 4,4′-DPE than PSQ, BSQ. Percentage of ROS was increased to 60% in WI38 cells after olaparib treatment. When PSQ, BSQ and 4,4′-DPE were applied separately on these oxidative-stress-induced cells for 48 h, the overall percentage of ROS was decreased to 39.3%, 45.6% and 19.3% respectively. This 4,4′-DPE was found to be more effective in inhibiting senescence by removing ROS as compared to squalene. Therefore, this 4,4′-DPE would be new potent senotherapeutic agent for pharmaceuticals and dermatological products.

旨在为油用牡丹的品种选育、牡丹籽油的营养评价和产地溯源提供参考信息,采用气相色谱-质谱法对4个油用牡丹主产地（河南洛阳、山东菏泽、安徽亳州和甘肃兰州）的凤丹牡丹籽油和紫斑牡丹籽油的脂肪酸组成和角鲨烯含量进行检测，并对牡丹籽油的脂肪酸及角鲨烯含量与环境因子的相关性进行分析。结果表明：牡丹籽油中含有11种脂肪酸，以α-亚麻酸、油酸和亚油酸为主；8个牡丹籽油样品中的脂肪酸相对含量及角鲨烯含量存在差异，其中相同产地的凤丹牡丹籽油中的油酸相对含量均显著低于紫斑牡丹籽油的（p

Coconut (Cocos nucifera) leaves, an unutilized resource, enriched with valuable bioactive compounds. Spectral analysis of purified pentane fraction of coconut leaves revealed the presence of a squalene analog named 4,4′-diapophytofluene or in short 4,4′-DPE (C30H46). Pure squalene standard (PSQ) showed cytotoxicity after 8 µg/ml concentration whereas 4,4′-DPE exhibited no cytotoxic effects up to 16 µg/ml concentration. On senescence-induced WI38 cells, 4,4′-DPE displayed better percentage of cell viability (164.5% at 24 h, 159.4% at 48 h and 148% at 72 h) compared to PSQ and BSQ (bio-source squalene) with same time duration. Similar trend of result was found in HaCaT cells. SA-β-gal assay showed that number of β-galactosidase positive cells were significantly decreased in senescent cells (WI38 and HaCaT) after treated with 4,4′-DPE than PSQ, BSQ. Percentage of ROS was increased to 60% in WI38 cells after olaparib treatment. When PSQ, BSQ and 4,4′-DPE were applied separately on these oxidative-stress-induced cells for 48 h, the overall percentage of ROS was decreased to 39.3%, 45.6% and 19.3% respectively. This 4,4′-DPE was found to be more effective in inhibiting senescence by removing ROS as compared to squalene. Therefore, this 4,4′-DPE would be new potent senotherapeutic agent for pharmaceuticals and dermatological products. [ABSTRACT FROM AUTHOR]

Squalene-based adjuvant compositions that can provide effective induction of specific humoral immune response have been developed. Recombinant receptor-binding domain (RBD) of surface S-protein of SARS-CoV-2 was used to evaluate the properties of the composition. Immunization of mice with the developed squalene-based compositions in combination with RBD allows obtaining high titers of specific antibodies: from 105 to 2×106. The blood sera from immunized mice exhibit neutralizing activity against SARS-CoV-2 Delta variant (B.1.617.2) with a titer up to 1:2000. [ABSTRACT FROM AUTHOR]

Background: While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. Methods: We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. Results: Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. Conclusions: Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment. [ABSTRACT FROM AUTHOR]

Squalene (SQ) has been documented in the past for its ability to reduce inflammation, but its mechanism needs more information. In this study, we investigated squalene as an anti-inflammatory drug candidate and the framework involved in treating inflammation (INF) using the network pharmacology concept. The molecular targets of SQ and INF that are available in databases and the overlaps between these targets were demonstrated using InteractiVenn. The protein-protein networks were generated that in turn revealed several key targets and were further processed with Cytoscape. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) studies were performed. We also performed molecular docking tests that validated the binding affinity of molecular targets and drugs. A total of 100 SQ targets and 11,417 INF-related targets yielded 93 overlapping targets. Seven core targets, CRHR1, EGFR, ERBB2, HIF1A, SLC6A3, MAP2K1, and F2R were found to be relevant with respective to SQ’s anti-inflammatory activity. The underlying mechanism of SQ with regard to INF was interpreted by analyzing various enrichment analyses along with the KEGG pathway. In conclusion, SQ played a vital role in the management of INF by regulating CRHR1, EGFR, ERBB2, HIF1A, SLC6A3, MAP2K1, and F2R. The research outcomes are crucial as they offer significant insights into the use of SQ for combating inflammation. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a simultaneous analytical method for the determination of lignans, tocols, phytosterols, and squalene using high-performance liquid chromatography coupled with a diode array and fluorescence detector (HPLC-DAD-FLD). The method employed a VertisepTM UPS silica HPLC column (4.6 × 250 mm, 5 µm) with a mobile phase mixture of n-hexane/tetrahydrofuran/2-propanol. This approach enabled the simultaneous analysis of ten compounds within 22 min. The linear correlation (R2) exceeded 0.9901. The limit of detection (LOD) and limit of quantitation (LOQ) were up to 0.43 µg mL−1 for lignans and tocopherols and up to 326.23 µg mL−1 for phytosterol and squalene. The precision and accuracy of the intra-day and inter-day variation were less than 1.09 and 3.32% relative standard deviations (RSDs). Furthermore, the developed method was applied for the analysis of targeted compounds in twenty-eight sesame oil samples (1775–8965 µg g−1 total lignans, 29.7–687.9 µg g−1 total tocopherols, 2640–9500 µg g−1 phytosterol, and 245–4030 µg g−1 squalene). The HPLC method that has been developed was proven to be a reliable and effective tool for the determination of those functional compounds among sesame oil samples. [ABSTRACT FROM AUTHOR]

MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms. [ABSTRACT FROM AUTHOR]

Thraustochytrids, as a distinct group of heterotrophic protists, have garnered considerable attention owing to their remarkable adaptability in extreme marine environments, pronounced capacity for metabolic regulation and prolific production of high-value metabolites. The taxonomic classification of these microorganisms presents a substantial challenge due to the variability in morphological characteristics under different culture conditions. And this undermines the efficacy of traditional classification systems on physiological and biochemical traits. The establishment of a polyphasic taxonomic system integrating genomic characteristics in the future will provide new avenues for more accurate classification and identification. Thraustochytrids can effectively accumulate bioactive substances such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), squalene and carotenoids. Through fermentation optimization and genetic modification, scientists have significantly enhanced the production of these metabolites. Moreover, the application of thraustochytrids in aquaculture, poultry and livestock feed has significantly improved animal growth and physiological indicators meanwhile increasing their DHA content. Natural bioactive substances in thraustochytrids, such as terpenoid compounds with antioxidant properties, have been proposed for application in the cosmetics industry. In the field of pharmacology, thraustochytrids have shown certain antiinflammatory and anti-cancer activities and provide potential for the development of new oral vaccines. Additionally, they can degrade various industrial and agricultural wastes for growth and fatty acid production, demonstrating their potential in environmental bioremediation. Therefore, thraustochytrids not only exhibit tremendous application potential in the field of biotechnology, but also hold significant value in environmental protection and commercialization. [ABSTRACT FROM AUTHOR]

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate–cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate–cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers. [ABSTRACT FROM AUTHOR]

Medicinal plants Highly aromatic crude materials are utilized for treating warts as an alternative medicine to surgical treatment because they can be permanently removed from the body. Thus, this investigation aimed to extract plant material from Calotropis procera leaves, describe the phytochemical screening, analyze anti-microbial activities, determine the functional groups in FTIR, and identify the chemical compounds in GC-MS. The PH, specific gravity, and viscosity of the crude extracts of Calotropis procera were determined at 4.5, 0.79, and 0.49, respectively. Analyze the solubility of crude extracts; ethanol can dissolve while water does not. Flavonoids, alkaloids, phenols, tannins, and saponins were also present in the phytochemical screening tests of the Calotropis procera extracts, triterpenoids, terpenoids, and steroids were not present in the crude extract. Flavonoids, alkaloids, phenols, tannins, and saponins are the primary phytochemical components found in therapeutic plant material. The Calotropis procera crude extracts analyzed for functional groups by FT-IR contained a hydroxyl group, alkane, carbonyl, aldehyde, ketone, phenols, ester, alcohol, and methylene. The chemical compounds analyzed by GC-MS of Calotropis procera crude material were found to have 22 main compounds. Of 22 compounds, 5 compounds are active ingredients for the applications of medical purposes. The bioactive compounds found in the Calotropis procera plant extract are neophytadiene, hexahydrofarnesyl, lanosterol, 2,4-dimethylbenzo [H]quinolone, and squalene. Those bioactive compounds have anti-bacterial, analgesic, antipyretic, anti-inflammatory, antimicrobial, antioxidant, antiviral, and anti-cancer properties. In an in vitro antimicrobial activity test, the crude extract effectively inhibited more gram-positive bacteria than gram-negative bacteria. This collective reason is why the traditional therapist uses this Calotropis procera plant for the treatment of warts.

Abstract This study evaluated the oil content obtained from andiroba seeds by pressurized n-propane at different conditions of temperature (25, 35, and 45 °C) and pressure (40, 60, and 80 bar), and conventional extraction technique using n-hexane as the solvent. Kinetic extraction curves were fitted using Sovová’s mathematical model. The chemical characterization of the oil was reported as well as the protein content in the extraction by-product. Pressurized extractions conducted at 25 °C provided the highest oil recovery (~45 wt%) from the seeds. The increase in pressure at 25 ºC favored obtaining oil with higher Stigmasterol contents, however, the Squalene content was higher in the oil obtained at 40 bar. The oils with the highest concentration phenolic compounds and antioxidant activity were obtained at 80 bar. Extraction with n-propane provided oils with higher levels of phenolic compounds, however, with antioxidant activity similar to conventional extraction. For all evaluated extractions, the product showed a predominance of oleic and palmitic acids, with similar values of oxidative stability. The extraction of the by-product with the highest soluble protein content was obtained under mild processing conditions (25 °C and 40 bar) with n-propane.

Pumpkin belongs to the family of Cucurbitaceae, which comprises several species that has economical as well as agronomical importance. All parts of pumpkin are edible and laden with beneficial neutraceutical compounds. Pumpkin seeds are valuable source protein which can help in eradicating protein malnutrition and lipids (rich in PUFAs) contains essential as well as non essential fatty acids which prevents from various ailments like cancer and other cardiovascular diseases. Since, seeds of pumpkin are abundant in macro (magnesium, phosphorous, potassium, sodium and calcium) and micro minerals (iron, copper, manganese, zinc and selenium), they can be used as an incredible dietary supplement which in turn helps in curbing various deficiency disorders. This review enlightens the characteristics of pumpkin seeds, process of valorization of pumpkin seeds and the effect of processing on their nutritional composition which have been studied currently with the aim to use this wonder seeds for human wellbeing. Pumpkin seeds possess many bioactive compounds like polyphenols, flavonoids, phytosterols and squalene which makes it a lucrative raw material for pharmacological and food industries. Pumpkin seeds work as anti-depressant and helps majorly in the treatment of benign prostate hyperplasia (BHP). Daily consumption of pumpkin seeds can reduce the chances of Alzheimer's and Parkinson's disease. Pumpkin seeds are rich in tocopherols and can be used for oil extraction for edible purposes and utilized in other food formulations for future use.

Abstract In this study, the efficacy of sublingual squalene in decreasing the mortality rate among patients with COVID-19 was investigated. Squalene was extracted from pumpkin seed oil with a novel method. Then, the microemulsion form of squalene was prepared for sublingual usage. In the clinical study, among 850 admitted patients, 602 eligible COVID-19 patients were divided in two groups of control (N = 301) and cases (N = 301) between Nov 2021 and Jan 2022. Groups were statistically the same in terms of age, sex, BMI, lymphocyte count on 1st admission day, hypertension, chronic kidney disease, chronic respiratory disease, immunosuppressive disease, and required standard treatments. The treatment group received five drops of sublingual squalene every 4 h for 5 days plus standard treatment, while the control group received only standard treatment. Patients were followed up for 30 days after discharge from the hospital. The sublingual form of squalene in the microemulsion form was associated with a significant decrease in the mortality rate (p

Celastrus paniculatus, a medicinal plant with diverse therapeutic activities, is known as 'malkangani' in the traditional medicine system of India, Ayurveda. It is well known for its memory‐enhancing potential. The reported work involves the gas chromatography‐mass spectrophotometric analysis of cold‐pressed seed oil of Celastrus paniculatus. It revealed the presence of components such as monosaturated fatty acids, polyunsaturated long‐chain fatty acids, and their derivatives. It also showed the presence of terpenes such as squalene, β amyrone, β amyrin acetate, and long‐chain hydrocarbons. Among all the constituents, squalene was found to be a major component. Hence, considering the potential pharmacological actions of squalene, a high‐performance thin‐layer chromatographic (HPTLC) method has been developed for its quantification and subsequently validated as per the International Conference of Harmonization guidelines. A HPTLC fingerprint of oil was obtained on pre‐coated silica gel 60 F254 aluminum sheets, using n‐hexane‐diethyl ether‐glacial acetic acid (7:3:0.05 v/v/v). A densitometric scan was performed at 470 nm after derivatization with vanillin sulphuric acid to quantify squalene. A well‐resolved squalene peak was obtained at a retardation factor of 0.85. It is a simple approach for the estimation of squalene in Celastrus paniculatus seed oil for quality control. [ABSTRACT FROM AUTHOR]

The article describes a novel active ingredient derived from Epilobium angustifolium that can provide a solution for impure and oily skin. The active ingredient regulates sebum production, combats bacterial virulence, and reduces squalene oxidation. A study shows that the extract can improve the appearance of impure and oily skin. The active ingredient reduces lipid content in the sebaceous glands and decreases skin shine. The effectiveness of the plant extract in treating oily skin was confirmed in a clinical study with Asian women. The results demonstrate that the plant extract offers a promising solution for the treatment of oily skin. [Extracted from the article]

While the ubiquitous beauty filter trend on social media has led individuals to seek digital enhancements for flawless skin, it is important to acknowledge the reality of blemish-prone and oily skin conditions. The article explores a novel skincare ingredient obtained from Epilobium angustifolium, commonly known as fireweed, as a solution to these skin concerns. The study focuses on improving blemishes by regulating sebum production, addressing bacterial virulence, and reducing squalene oxidation. An innovative ex vivo model was developed to assess the effects of the new ingredient on sebum lipids produced in the sebaceous gland. The results showed a significant reduction in lipid content following treatment with the new ingredient. The herbal active ingredient was also found to significantly reduce the lipase activity of bacteria, thereby reducing their virulence, and to contribute to sebum quality by reducing squalene oxidation. An in vivo study on women with oily skin demonstrated a significant improvement in skin shininess. The results of the study demonstrate that Epilobium angustifolium extract may provide an effective solution to blemish-prone and oily skin, meeting the needs of consumers seeking authentic beauty through healthier and more radiant skin. [ABSTRACT FROM AUTHOR]

Following the idea of a circular bioeconomy, the use of side streams as substitutes for cultivation media (components) in bioprocesses would mean an enormous economic and ecological advantage. Costly compounds in conventional media for the production of the triterpene squalene in thraustochytrids are the main carbon source and complex nitrogen sources. Among other side streams examined, extracts from the spent mycelium of the basidiomycete Pleurotus ostreatus were best-suited to acting as alternative nitrogen sources in cultivation media for thraustochytrids. The total nitrogen (3.76 ± 0.01 and 4.24 ± 0.04%, respectively) and protein (16.47 ± 0.06 and 18.57 ± 0.18%, respectively) contents of the fruiting body and mycelium were determined. The fungal cells were hydrolyzed and extracted to generate accessible nitrogen sources. Under preferred conditions, the extracts from the fruiting body and mycelium contained 73.63 ± 1.19 and 89.93 ± 7.54 mM of free amino groups, respectively. Cultivations of Schizochytrium sp. S31 on a medium using a mycelium extract as a complex nitrogen source showed decelerated growth but a similar squalene yield (123.79 ± 14.11 mg/L after 216 h) compared to a conventional medium (111.29 ± 19.96 mg/L, although improvable by additional complex nitrogen source). [ABSTRACT FROM AUTHOR]

Cholesterol present in food of animal origin is a precursor of oxysterols (COPs), whose high intake through diet can be associated with health implications. Evaluation of the content of these contaminants in food is associated with many analytical problems. This work presents a GC-TOF/MS method for the simultaneous determination of squalene, cholesterol and seven COPs (7-ketocholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, 25-hydroxycholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, cholestanetriol). The sample preparation procedure includes such steps as saponification, extraction and silylation. The method is characterized by high sensitivity (limit of quantification, 0.02–0.25 ng mL−1 for instrument, 30–375 μg kg of sample), repeatability (RSD 2.3–6.2%) and a wide linearity range for each tested compound. The method has been tested on eight different animal-origin products. The COP to cholesterol content ratio in most products is about 1%, but the profile of cholesterol derivatives differs widely (α = 0.01). In all the samples, 7-ketocholesterol is the dominant oxysterol, accounting for 31–67% of the total COPs level. The levels of the other COPs range between 0% and 21%. In none of the examined products are cholestanetriol and 25-hydroxycholesterol present. The amount of squalene, which potentially may inhibit the formation of COPs in food, ranges from 2 to 57 mg kg−1. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG‐rich (SGR) and SG‐poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex‐matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender‐related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender. [ABSTRACT FROM AUTHOR]

Amaranth, quinoa, and buckwheat are the representatives of pseudocereals, different parts and by-products of which are used in daily nutrition and food processing industry. However, only scarce information exists on the bioactivity of their oils. Thus, oils obtained from amaranth, buckwheat, and red, yellow, and white quinoa seeds were evaluated in terms of their nutritional (fatty acid profile, squalene), cytotoxic (against normal and neoplastic gastrointestinal, prostate, and skin cells), anti-inflammatory and antiradical (interleukin 6, TNF-alpha, nitric oxide, DPPH, Total phenolics, and superoxide dismutase) potential in the in vitro model. Linoleic (42.9–52.5%) and oleic (22.5–31.1%) acids were the two main unsaturated, while palmitic acid (4.9–18.6%) was the major saturated fatty acid in all evaluated oils. Squalene was identified in all evaluated oils with the highest content in amaranth oil (7.6 g/100 g), and the lowest in buckwheat oil (2.1 g/100 g). The evaluated oils exerted a high direct cytotoxic impact on cancer cells of different origins, but also revealed anti-inflammatory and antiradical potentials. Yellow quinoa oil was the most active, especially toward skin (A375; IC50 6.3 µg/mL), gastrointestinal (HT29 IC50 4.9 µg/mL), and prostate cancer cells (LNCaP IC50 7.6 µg/mL). The observed differences in the activity between the oils from the tested quinoa varieties deserve further studies. High selectivity of the oils was noted, which indicates their safety to normal cells. The obtained results indicate that the oils are good candidates for functional foods with perspective chemopreventive potential. [ABSTRACT FROM AUTHOR]

Terpenoids are enormous and different types of naturally occurring metabolites playing an important role in industrial applications. Cost-effective and sustainable production of terpenoids at commercial scale is the big challenge because of its low abundance from their natural sources. Metabolic and genetic engineering in microorganisms provide the ideal platform for heterologous overexpression protein systems. The photosynthetic green alga Chlamydomonas reinhardtii is considered as a model host for the production of economic and sustainable terpenoids, but the regulation mechanism of their metabolisms is still unclear. In this study, we have investigated the genetic and metabolic synthetic engineering strategy of MYB transcriptional factors (MYB TFs) in terpenoids' synthesis from C. reinhardtii for the first time. We heterologous overexpressed MYB TFs, specifically SmMYB36 from Salvia miltiorrhiza in C. reinhardtii. MYB upregulated the key genes involved in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Expression of the SQS gene, which is involved in the downstream triterpenoid synthesis pathway, highly accumulated in MYB-overexpression lines of C. reinhardtii. The contents of squalene increased about 90.20 μg/g in MYB-overexpressed lines. Our results propose the rerouting of the carbon flux toward the biosynthesis of triterpenoids upon overexpression of MYB TFs in C. reinhardtii. Our study suggests imperative novel understandings into the regulation mechanisms of C. reinhardtii triterpenoid metabolism through MYB TFs in photosynthetic green microalgae C. reinhardtii. The role of MYB TFs is investigated for the first time in C. reinhardtii, and provides a prodigious potential for recognizing important transcriptional regulators of the MEP pathway as goals for prospective metabolic and genetic manipulation investigation for increased production of triterpenoids. [ABSTRACT FROM AUTHOR]

In this study, the efficacy of sublingual squalene in decreasing the mortality rate among patients with COVID-19 was investigated. Squalene was extracted from pumpkin seed oil with a novel method. Then, the microemulsion form of squalene was prepared for sublingual usage. In the clinical study, among 850 admitted patients, 602 eligible COVID-19 patients were divided in two groups of control (N = 301) and cases (N = 301) between Nov 2021 and Jan 2022. Groups were statistically the same in terms of age, sex, BMI, lymphocyte count on 1st admission day, hypertension, chronic kidney disease, chronic respiratory disease, immunosuppressive disease, and required standard treatments. The treatment group received five drops of sublingual squalene every 4 h for 5 days plus standard treatment, while the control group received only standard treatment. Patients were followed up for 30 days after discharge from the hospital. The sublingual form of squalene in the microemulsion form was associated with a significant decrease in the mortality rate (p < 0.001), in which 285 (94.7%) cases were alive after one month while 245 (81.4%) controls were alive after 1 month of discharge from the hospital. In addition, squalene appears to be effective in preventing re-hospitalization due to COVID-19 (p < 0.001), with 141 of controls (46.8%) versus 58 cases (19.3%). This study suggests sublingual squalene in the microemulsion as an effective drug for reducing mortality and re-hospitalization rates in COVID-19 patients. Trial Registration Number: IRCT20200927048848N3. [ABSTRACT FROM AUTHOR]

Filamentous fungi produce numerous uncharacterized natural products (NPs) that are often challenging to characterize because of cryptic expression in laboratory conditions. Previously, we have successfully isolated novel NPs by expressing fungal artificial chromosomes (FACs) from a variety of fungal species into Aspergillus nidulans. Here, we demonstrate a twist to FAC utility wherein heterologous expression of a Pseudogymnoascus destructans FAC in A. nidulans altered endogenous terpene biosynthetic pathways. In contrast to wild type, the FAC transformant produced increased levels of squalene and aspernidine type compounds, including three new nidulenes (1- 2, and 5), and lost nearly all ability to synthesize the major A. nidulans characteristic terpene, austinol. Deletion of a squalene synthase gene in the FAC restored wild-type chemical profiles. The altered squalene to farnesyl pyrophosphate ratio leading to synthesis of nidulenes and aspernidines at the expense of farnesyl pyrophosphate- derived austinols provides unexpected insight into routes of terpene synthesis in fungi. [ABSTRACT FROM AUTHOR]

The triterpene squalene is widely used in the food, cosmetics and pharmaceutical industries due to its antioxidant, antistatic and anti-carcinogenic properties. It is usually obtained from the liver of deep sea sharks, which are facing extinction. Alternative production organisms are marine protists from the family Thraustochytriaceae, which produce and store large quantities of various lipids. Squalene accumulation in thraustochytrids is complex, as it is an intermediate in sterol biosynthesis. Its conversion to squalene 2,3-epoxide is the first step in sterol synthesis and is heavily oxygen dependent. Hence, the oxygen supply during cultivation was investigated in our study. In shake flask cultivations, a reduced oxygen supply led to increased squalene and decreased sterol contents and yields. Oxygen-limited conditions were applied to bioreactor scale, where squalene accumulation and growth of Schizochytrium sp. S31 was determined in batch, fed-batch and continuous cultivation. The highest dry matter (32.03 g/L) was obtained during fed-batch cultivation, whereas batch cultivation yielded the highest biomass productivity (0.2 g/L*h−1). Squalene accumulation benefited from keeping the microorganisms in the growth phase. Therefore, the highest squalene content of 39.67 ± 1.34 mg/g was achieved by continuous cultivation (D = 0.025 h−1) and the highest squalene yield of 1131 mg/L during fed-batch cultivation. Volumetric and specific squalene productivity both reached maxima in the continuous cultivation at D = 0.025 h−1 (6.94 ± 0.27 mg/L*h−1 and 1.00 ± 0.03 mg/g*h−1, respectively). Thus, the choice of a suitable cultivation method under oxygen-limiting conditions depends heavily on the process requirements. Key points: • Measurements of respiratory activity and backscatter light of thraustochytrids • Oxygen limitation increased squalene accumulation in Schizochytrium sp. S31 • Comparison of different cultivation methods under oxygen-limiting conditions [ABSTRACT FROM AUTHOR]

The aim of this research was to study the impact of squalene synthase gene silencing on the features of transgenic chrysanthemum plants, and on the synthesis of some sesquiterpenes—caryophyllene, germacrene and farnesene. We have cloned chrysanthemum squalene synthase gene cDNA (CmSQS) and obtained five lines stably transformed with vector for CmSQS silencing. Silencing of CmSQS gene transcription was detected in all five transgenic lines, the decrease in the squalene content was found in three of them, by 1.8–2.0 times depending on the line. The content of triterpenes α- and β-amirin, derivatives of squalene, clearly correlated with its content in plants. The β-caryophyllene, germacrene D and β-farnesene were identified in chrysanthemum using GC-MS analysis; the content of these compounds in transgenic plants did not change appreciably compared to control ones. Silencing of squalene synthase had no effect on plants morphology. In two transgenic lines, a decrease in growth rate relative to non-transgenic plants was observed; the growth rate of three other lines did not differ from the control. Thus, in our experiments no well-defined relationship between CmSQS gene transcription level, the content of squalene and studied sesquiterpenes was found. The obtained data provide additional information on mechanisms of plant secondary metabolism regulation including the relation between β-caryophyllene, germacrene D and β-farnesene content with squalene synthesis level. [ABSTRACT FROM AUTHOR]

Intramembrane proteolysis regulates important processes such as signaling and transcriptional and posttranslational abundance control of proteins with key functions in metabolic pathways. This includes transcriptional control of mevalonate pathway genes, thereby ensuring balanced biosynthesis of cholesterol and other isoprenoids. Our work shows that, at high cholesterol levels, signal peptide peptidase (SPP) cleaves squalene synthase (SQS), an enzyme that defines the branching point for allocation of isoprenoids to the sterol and nonsterol arms of the mevalonate pathway. This intramembrane cleavage releases SQS from the membrane and targets it for proteasomal degradation. Regulation of this mechanism is achieved by the E3 ubiquitin ligase TRC8 that, in addition to ubiquitinating SQS in response to cholesterol levels, acts as an allosteric activator of SPP-catalyzed intramembrane cleavage of SQS. Cellular cholesterol levels increase in the absence of SPP activity. We infer from these results that, SPP-TRC8 mediated abundance control of SQS acts as a regulation step within the mevalonate pathway. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OSA) presents a clinical challenge and has a low 5‐year survival rate. Currently, the lack of advanced stratification models makes personalized therapy difficult. This study aims to identify novel biomarkers to stratify high‐risk OSA patients and guide treatment. Methods: We combined 10 machine‐learning algorithms into 101 combinations, from which the optimal model was established for predicting overall survival based on transcriptomic profiles for 254 samples. Alterations in transcriptomic, genomic and epigenomic landscapes were assessed to elucidate mechanisms driving poor prognosis. Single‐cell RNA sequencing (scRNA‐seq) unveiled genes overexpressed in OSA cells as potential therapeutic targets, one of which was validated via tissue staining, knockdown and pharmacological inhibition. We characterized changes in multiple phenotypes, including proliferation, colony formation, migration, invasion, apoptosis, chemosensitivity and in vivo tumourigenicity. RNA‐seq and Western blotting elucidated the impact of squalene epoxidase (SQLE) suppression on signalling pathways. Results: The artificial intelligence‐derived prognostic index (AIDPI), generated by our model, was an independent prognostic biomarker, outperforming clinicopathological factors and previously published signatures. Incorporating the AIDPI with clinical factors into a nomogram improved predictive accuracy. For user convenience, both the model and nomogram are accessible online. Patients in the high‐AIDPI group exhibited chemoresistance, coupled with overexpression of MYC and SQLE, increased mTORC1 signalling, disrupted PI3K–Akt signalling, and diminished immune infiltration. ScRNA‐seq revealed high expression of MYC and SQLE in OSA cells. Elevated SQLE expression correlated with chemoresistance and worse outcomes in OSA patients. Therapeutically, silencing SQLE suppressed OSA malignancy and enhanced chemosensitivity, mediated by cholesterol depletion and suppression of the FAK/PI3K/Akt/mTOR pathway. Furthermore, the SQLE‐specific inhibitor FR194738 demonstrated anti‐OSA effects in vivo and exhibited synergistic effects with chemotherapeutic agents. Conclusions: AIDPI is a robust biomarker for identifying the high‐risk subset of OSA patients. The SQLE protein emerges as a metabolic vulnerability in these patients, providing a target with translational potential. [ABSTRACT FROM AUTHOR]

Acne is a chronic inflammatory disease of pilosebaceous units. This study aims to analyze the composition of skin surface lipids in patients with acne compared to controls to correlate the severity of acne. The severity of acne was graded according to the standard grading system in clinical terms. Skin surface lipid samples were collected by rubbing the skin over the face with a swab soaked in hexane for a minute. The analysis was performed by UFLC with a UV detector. Subjects with acne were found to have a significantly higher quantity of squalene (p < 0.001) in the sebum. The free fatty acids (FFAs)—specifically, oleic acid (p = 0.002) and stearic acid (p = 0.013)—were elevated, whereas linoleic acid (p < 0.001) was decreased in the sebum of acne patients compared to controls. The mean scores of squalene were higher as the clinical grade of acne increased. However, the free fatty acids did not show a significant correlation with the clinical grading. The study revealed an increased level of skin surface lipids in patients with acne vulgaris, particularly in FFAs, conforming the role of sebum in the pathogenesis of acne. A specific therapeutic agent may play a crucial role in the management of acne. [ABSTRACT FROM AUTHOR]

Copyright of Food Science & Technology & Economy is the property of Grain Science & Technology & Economy Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Constructing efficient cell factories for product synthesis is frequently hampered by competing pathways and/or insufficient precursor supply. This is particularly evident in the case of triterpenoid biosynthesis in Yarrowia lipolytica, where squalene biosynthesis is tightly coupled to cytosolic biosynthesis of sterols essential for cell viability. Here, we addressed this problem by reconstructing the complete squalene biosynthetic pathway, starting from acetyl-CoA, in the peroxisome, thus harnessing peroxisomal acetyl-CoA pool and sequestering squalene synthesis in this organelle from competing cytosolic reactions. This strategy led to increasing the squalene levels by 1,300-fold relatively to native cytosolic synthesis. Subsequent enhancement of the peroxisomal acetyl-CoA supply by two independent approaches, 1) converting cellular lipid pool to peroxisomal acetyl-CoA and 2) establishing an orthogonal acetyl-CoA shortcut from CO2-derived acetate in the peroxisome, further significantly improved local squalene accumulation. Using these approaches, we constructed squalene-producing strains capable of yielding 32.8 g/L from glucose, and 31.6 g/L from acetate by employing a cofeeding strategy, in bioreactor fermentations. Our findings provide a feasible strategy for protecting intermediate metabolites that can be claimed by multiple reactions by engineering peroxisomes in Y. lipolytica as microfactories for the production of such intermediates and in particular acetyl-CoA- derived metabolites. [ABSTRACT FROM AUTHOR]

Squalene, which is a natural triterpenoid unsaturated hydrocarbon, is abundant in shark liver and plant seeds. Squalene has various physiological functions such as being anti-inflammatory and antioxidant. This paper reviews the physiological functions of squalene and its application prospects in livestock and poultry production, with a view to providing a theoretical basis for its indepth application in animal husbandry. [ABSTRACT FROM AUTHOR]

Background: Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids. Result: In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. The sgRNA were designed based on the active site residues. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. The results showed that deletion of PcSE inhibited triterpene synthesis. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach. Conclusion: The findings from this study provide a foundation for further studies on heterologous biosynthesis of P. cocos secondary metabolites. Highlights: The gene of squalene epoxidase in P. cocos was identified. Molecular docking was used to predict the amino acid active site of PcSE. Establishment of a CRISPR/Cas9 gene editing system in P. cocos. Function validation of PcSE on triterpene synthesis by gene deletion. [ABSTRACT FROM AUTHOR]

The accumulation of ginsenosides (triterpenic saponins) was determined in Panax quinquefolium hairy root cultures subjected to an elicitation process using carvacrol at 5, 10, 25, 50, 100, 250, and 500 μM concentrations during 24 and 72 h exposure. This study was the first one in which carvacrol was applied as an elicitor. The content of eight ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, and Re, was determined using HPLC analysis. Moreover, the quantitative RT-PCR method was applied to assess the relative expression level of farnesyl diphosphate synthase, squalene synthase, and dammarenediol synthase genes in the studied cultures. The addition of carvacrol (100 μM) was an effective approach to increase the production of ginsenosides. The highest content and productivity of all detected saponins were, respectively, 20.01 mg∙g−1 d.w. and 5.74 mg∙L−1∙day−1 after 72 h elicitation. The production profile of individual metabolites in P. quinquefolium cultures changed under the influence of carvacrol. The biosynthesis of most examined protopanaxadiol derivatives was reduced under carvacrol treatment. In contrast, the levels of ginsenosides belonging to the Rg group increased. The strongest effect of carvacrol was noticed for Re metabolites, achieving a 7.72-fold increase in comparison to the control. Saponin Rg2, not detected in untreated samples, was accumulated after carvacrol stimulation, reaching its maximum concentration after 72 h exposure to 10 μM elicitor. [ABSTRACT FROM AUTHOR]