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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.

Organic molecules in the environment oxidatively degrade by a variety of free radical, microbial, and biogeochemical pathways. A significant pathway is heterogeneous autoxidation, in which degradation occurs via a network of carbon and oxygen centered free radicals. Recently, we found evidence for a new heterogeneous autoxidation mechanism of squalene that is initiated by hydroxyl (OH) radical addition to a carbon-carbon double bond and apparently propagated through pathways involving Criegee Intermediates (CI) produced from β-hydroxy peroxy radicals (β-OH-RO2•). It remains unclear, however, exactly how CI are formed from β-OH-RO2•, which could occur by a unimolecular or bimolecular pathway. Combining kinetic models and multiphase OH oxidation measurements of squalene, we evaluate the kinetic viability of three mechanistic scenarios. Scenario 1 assumes that CI are formed by the unimolecular bond scission of β-OH-RO2•, whereas Scenarios 2 and 3 test bimolecular pathways of β-OH-RO2• to yield CI. Scenario 1 best replicates the entire experimental data set, which includes effective uptake coefficients vs [OH] as well as the formation kinetics of the major products (i.e., aldehydes and secondary ozonides). Although the unimolecular pathway appears to be kinetically viable, future high-level theory is needed to fully explain the mechanistic relationship between CI and β-OH-RO2• in the condensed phase.

Squalene synthase (SQS) is the most direct key enzyme regulating squalene synthesis. To better understand the regulatory mechanisms of squalene biosynthesis, a 1423-bp long promoter region of the CoSQS gene was isolated from Camellia oleifera. Plant CARE and PLACE analysis affirmed the existence of the core promoter elements such as TATA and CAAT boxes and transcription factor binding sites like W-box and MYB in the isolated sequence. Exogenous factors regulating the CoSQS promoter were obtained by using Yeast one-hybrid screening, and the key transcription factor CoWRKY15 was found. AOS (Antibody Optimization System) analysis showed that CoWRKY15 had the highest interactions with a confidence level of 0.9026. Bioinformatics analysis showed that CoWRKY15 belonged to class 2 of the WRKY gene family. The results of subcellular localization showed that CoWRKY15 functioned in the nucleus. The results of CoWRKY15 promoter analysis showed that 8 out of 14 cis-elements with annotatable functions were related to the light response. The region of the CoSQS promoter that interacts with CoWRKY15 is −186 bp~−536 bp. The histochemical assay and squalene content suggested that the CoSQS promoter could drive the expression of GUS gene and specific promotion of CoSQS expression. It was found that CoWRKY15 could act on the −186 bp~−536 bp CoSQS promoter to regulate the expression of CoSQS and the content of squalene in C. oleifera seed kernels. [ABSTRACT FROM AUTHOR]

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]

This study aimed to investigate the characteristics of different varieties of camellia oils and their diacylglycerol (DAG)-enriched derivatives in terms of triacylglycerol (TAG) species, bioactive components, volatile compounds, and antioxidant activity. Six types of camellia oils, including C. oleifera (C.O), C. semiserrata (C.S), C. gauchowensis (C.G), along with commercially refined C. oleifera oil (C-C.O) and its DAG-enriched counterparts (at 40% and 80% enrichment), were analyzed and compared. Unique patterns of TAG profiles, fatty acid distributions on different glycerol backbones, tocopherol, squalene, total polyphenols, and volatile compounds were observed, suggesting that these characteristics can be utilized as a criterion to differentiate them. DAG-enriched oils exhibited increased levels of unsaturated fatty acids (UFAs) compared to C-C.O, albeit with decreased contents of tocopherol, squalene, and total polyphenols. Moreover, diverse volatile compounds were identified across all types of camellia oils, among which the DAG-enriched oils had distinct distribution characteristics compared with their crude oils, indicating the influence of the enrichment process on volatile compounds. Furthermore, DAG-enriched oils demonstrated reduced antioxidant activity abilities compared to their counterparts, with the highest activity observed in C.O, followed by C.G. Additionally, strong correlations were observed between antioxidant activity and tocopherol, as well as squalene content. [ABSTRACT FROM AUTHOR]

This study investigated whether pre-treating sesame (Sesamum indicum L.) seeds with a combination of acid-soaking and microwave-heating could significantly enhance the quality of the resulting sesame oil, particularly by increasing its content of functional compounds such as lignans, tocopherol, phytosterol, and squalene. The study revealed that soaking the sesame seeds in a solution of HCl and citric acid, along with microwave-heating, significantly increased the content of these compounds. The detected ranges were sesamin (1365–6927 µg g−1), sesamolin (605–3493 µg g−1), tocopherol (69.31–282.76 µg g−1), asarinin (ND–383.52 µg g−1), sesamol (ND–49.59 µg g−1), phytosterol (3690–6201 µg g−1), and squalene (532−1628 µg g−1). Additionally, the study found that the pre-treatment of sesame seeds had a minimal effect on the fatty acid composition, antioxidant activity (92.94–95.08% DPPH scavenging activity), and oxidative stability (2.13–2.90 mg MDA kg−1 oil). This is the first study to demonstrate that using acid-soaking and microwave-heating to prepare sesame seeds can produce sesame oil enriched with functional compounds, potentially benefiting cosmetic, pharmaceutical, and health applications. [ABSTRACT FROM AUTHOR]

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]

Balanites aegyptiaca is a multipurpose fruit tree that grows wild in many arid and semi-arid African areas; however, recent domestication efforts have been undertaken to protect the species from the threat of urbanization and climate change. Within this context, the impact of the domestication of Algerian B. aegyptiaca was evaluated on its seed oil, which is already valued as food. Hence, oils from wild and domesticated trees were comparatively investigated for their physicochemical and compositional quality. Both oil types had a good oxidative stability and met the requirements for human consumption in terms of the saponification index, the free acidity, and the peroxide value. Moreover, they showed a comparable FA composition, with high levels of oleic and linoleic acids, which are beneficial for the consumer's health. Domestication led to a statistically significant decrease in the tocopherols and polyphenols in the oil. The phytosterols and squalene were slightly lower in the domesticated oil than in the wild relative, although no statistically significant differences were observed. A comparable mineral profile was revealed and the minimal variations in the trace elements between the oils could be related to the natural variability in the seeds. Hopefully, this study will encourage the domestication of B. aegyptiaca as a sustainable strategy for enhancing its socioeconomic value in Algerian rural areas. [ABSTRACT FROM AUTHOR]

Abstract 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 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.

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]

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]

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]

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]

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]

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.

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

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.

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]

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]

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]

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]

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]

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.

Squalene is a highly sought-after triterpene compound in growing demand, and its production offers a promising avenue for circular economy practices. In this study, we applied metabolic engineering principles to enhance squalene production in the nonconventional yeast Yarrowia lipolytica, using waste cooking oil as a substrate. By overexpressing key enzymes in the mevalonate pathway — specifically ERG9 encoding squalene synthase, ERG20 encoding farnesyl diphosphate synthase, and HMGR encoding hydroxy-methyl-glutaryl-CoA reductase — we achieved a yield of 779.9 mg/L of squalene. Further co-overexpression of DGA1, encoding diacylglycerol acyltransferase, and CAT2, encoding carnitine acetyltransferase, in combination with prior metabolic enhancements, boosted squalene production to 1381.4 mg/L in the engineered strain Po1g17. To enhance the supply of the precursor acetyl-CoA and inhibit downstream squalene conversion, we supplemented with 6 g/L pyruvic acid and 0.7 mg/L terbinafine, resulting in an overall squalene titer of 2594.1 mg/L. These advancements underscore the potential for sustainable, large-scale squalene production using Y. lipolytica cell factories, contributing to circular economy initiatives by valorizing waste materials.

Although there may be a number of disadvantages, many patients prefer the traditional medication over surgical wart therapy since it may permanently remove the abscess from the body. The roots of the Ficifolius A. Rich plant are one of the native plants used in Ethiopia for traditional wart treatment. Therefore, the main goal of the research was to examine the phytochemical characteristics, identify the chemical compounds, and assess the antimicrobial effectiveness of the previously described plant root extract against gram-positive Staphylococcus aureus and gram-negative Escherichia coli pathogenic bacteria. Consequently, phytochemical characteristics such as tannins, alkaloids, flavonoids, phenols, and saponin were perceived, which inferred the therapeutic implications of root extracts. Furthermore, gas chromatography-mass spectrometry investigations identified a number of chemical components, including the particular antiviral substance Squalene. Moreover, antibacterial test results showed that the growth of gram-positive and gram-negative bacteria was inhibited with the application of crude extract. Generally, Ficifolius A. rich root extract could be effectively utilized for the treatment of anal warts.

Oil was extracted from melon seeds with three different methods (Soxhlet, cold-pressed, aqueous enzymatic extraction), aiming to evaluate its physicochemical properties and oxidative stability. The melon seed oil contained high levels of linoleic acid (53.6 %–70.8 %, w/w), squalene (101.1–164.7 mg/100 g), and β-sitosterol (119.5–291.9 mg/100 g). Results showed that the choice of the extraction method did not alter the fatty acid composition, but impacted on the physicochemical properties, the content of bioactive compounds and oxidative stability of the oil. Specifically, melon seed oil obtained by aqueous enzymatic extraction (AEE) exhibited higher tocopherol content and better oxidative stability compared to the oil obtained by other two extraction methods. Overall, AEE is a promising oil extraction method and could be an alternative to conventional oil extraction methods that could be implemented for the production of high-quality melon seed oil.

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

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H2O2)-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets.

Acne affects 1 in 10 people globally, often resulting in disfigurement. The disease involves excess production of lipids, particularly squalene, increased growth of Cutibacterium acnes, and a host inflammatory response with foamy macrophages. By combining single-cell and spatial RNA sequencing as well as ultrahigh-resolution Seq-Scope analyses of early acne lesions on back skin, we identified TREM2 macrophages expressing lipid metabolism and proinflammatory gene programs in proximity to hair follicle epithelium expressing squalene epoxidase. We established that the addition of squalene induced differentiation of TREM2 macrophages in vitro, which were unable to kill C. acnes. The addition of squalene to macrophages inhibited induction of oxidative enzymes and scavenged oxygen free radicals, providing an explanation for the efficacy of topical benzoyl peroxide in the clinical treatment of acne. The present work has elucidated the mechanisms by which TREM2 macrophages and unsaturated lipids, similar to their involvement in atherosclerosis, may contribute to the pathogenesis of acne.

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]

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]

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]

Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflammatory cytokines. JAK inhibitors, such as tofacitinib, bind to these enzymes which are coupled to receptors on cell surfaces and block the transcription of inflammatory cytokine-induced genes. The first topical applications are being marketed, yet insufficient effects regarding indications, such as alopecia areata, suggest that improved delivery technologies could help increase the efficacy. In this study, we used sulfated dendritic polyglycerol with caprolactone segments integrated in its backbone (dPGS-PCL), with a molecular weight of 54 kDa, as a degradable carrier to load and solubilize the hydrophobic drug tofacitinib (TFB). TFB loaded in dPGS-PCL (dPGS-PCL@TFB), at a 11 w/w% loading capacity in aqueous solution, showed in an ex-vivo human skin model better penetration than free TFB in a 30:70 (v/v) ethanol/water mixture. We also investigated the anti-inflammatory efficacy of dPGS-PCL@TFB (0.5 w/w%), dPGS-PCL, and free TFB in the water/ethanol mixture by measuring their effects on IL-6 and IL-8 release, and STAT3 and STAT5 activation in ex vivo skin models of simulated inflamed human skin. Our results suggest that dPGS-PCL@TFB reduces the activation of STAT3 and STAT5 by increasing the penetration of the tofacitinib. However, no statistically significant differences with respect to the inhibition of IL-6 and IL-8 were observed in this short incubation time. [ABSTRACT FROM AUTHOR]

Adulteration of camellia oils from the same source should be avoided. Hence, using chromatographic techniques, this study aimed to analyze and select components (fatty acids, squalene, tocopherols, and volatile substances) as variables for the precise characterization and discrimination of seven camellia oil varieties (Camellia gigantocarpa, Camellia vietnamensis, Camellia osmantha, Camellia nanyongensis, Camellia oleifera, Camellia semiserrata, and Camellia amplexicaulis). The principal component and hierarchical cluster analyses were performed to identify camellia seed oils, and their identification ability for different components was compared. All the components, except fatty acids, could clearly distinguish camellia oil varieties. However, when the fatty acids were combined with either squalene or tocopherol, the identification ability significantly improved. Identifying different varieties of camellia oils according to the abovementioned components provides a solid foundation for the fine processing of camellia oils, and the corresponding products should be developed according to these characteristics to enhance their value. [ABSTRACT FROM AUTHOR]

Terpenoids are used in various industries, and Saccharomyces cerevisiae is a promising microorganism for terpenoid production. Introducing the mevalonate (MVA) pathway into the mitochondria of a strain with an augmented inherent cytosolic MVA pathway increased terpenoid production but also led to the accumulation of toxic pyrophosphate intermediates that negatively affected terpenoid production. We first engineered the inherent MVA pathway in the cytosol and then introduced the MVA pathway into the mitochondria using several promoter combinations, considering the toxicity of pyrophosphate intermediates. However, the highest titer, 183 mg/L, tends to be only 5% higher than that of the strain that only augmented the inherent MVA pathway (SYCM1; 174 mg/L). Next, we hypothesized that, in addition to the toxicity of pyrophosphate, other compounds in the MVA pathway could affect the squalene titer. Thus, we constructed a combinatorial strain library expressing MVA pathway enzymes in the mitochondria with various promoter combinations. The highest squalene titer (230 mg/L) was 32% higher than that of SYCM1. The promoter set revealed that mitigation of mono- and pyrophosphate compound accumulation was important for mitochondrial usage. This study demonstrated that a combinatorial strain library is useful for discovering the optimal gene expression balance in engineering yeast. [ABSTRACT FROM AUTHOR]

Nowadays, acne vulgaris therapies are often unsuccessful. One of the responsible factors for the formation of comedones and inflammatory lesions could be the peroxidation of squalene, a hydrocarbon representing one of the major components of human sebum. This peroxidation is increased by solar irradiation. The purpose of this work was to set up an in vivo method for the extraction and quantification of squalene from acne skin and to correlate the results with biophysical skin parameters such as sebum amount, protein content and TEWL. Healthy volunteers were used as control. The results obtained demonstrated that acne-prone skin had a major quantity of squalene, and, in the stratum corneum area, its peroxide form is present. Moreover, Spearman's rank correlation showed a positive correlation between sebum content and peroxide squalene and between porphyrin intensity and peroxide squalene. [ABSTRACT FROM AUTHOR]

In recent years, there was an increase in the commercial offer of vegetable oils from unconventional sources, such as fruit, vegetable, and herb seeds. The paper presents a synthesis of available scientific information on 27 oils obtained from the seeds of 14 fruit species (apple, apricot, chokeberry, black berry, blackcurrant, blue berry, cherry, Japanese quince, pear, plum, quince, raspberry, rosehip, and strawberry), 8 vegetable species (broccoli, cabbage, carrot, cucumber, onion, parsley, radish, and tomato), and 5 herb species (basil, coriander, fennel, fenugreek, and perilla). A review of the literature showed that oil content in these seeds ranges from ca. 5% for fenugreek to over 55% for apricot kernels. A recommended n-6/n-3 fatty acid ratio below 4-5/1 was noted in 11 species. Japanese quince, blackcurrant, and fenugreek seed oils seem to be good sources of phytosterols. Radish seed oil was mostly abundant in tocols, Japanese quince seed oil in squalene, and blackcurrant seed oil in carotenoids. Unfortunately, actual data on the composition of these seed oils are highly variable, making it difficult to precisely identify the most nutritionally valuable oils. [ABSTRACT FROM AUTHOR]

Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.