Category: 434-16-2

Xiu, Xiang; Sun, Yi; Wu, Yaokang; Jin, Ke; Qu, Lisha; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Lv, Xueqin; Liu, Long published the artcile< Modular remodeling of sterol metabolism for overproduction of 7-dehydrocholesterol in engineered yeast>, Category: alcohols-buliding-blocks, the main research area is 7-Dehydrocholesterol; CRISPR-mediated regulatory system; Compartmentalization; Endoplasmic reticulum; Saccharomyces cerevisiae.

Vitamin D3 is a fat-soluble vitamin essential for the human body, and the biosynthesis of its precursor, 7-dehydrocholesterol (7-DHC), gains extensive attention. In this work, six genes (tHMG1, IDI1, ERG1, ERG11, ADH2, ERG7) and a transcription factor mutant UPC2G888A were overexpressed, increasing the 7-DHC titer from 1.2 to 115.3 mg/L. The CRISPR-mediated activation and repression systems were constructed and applied to the synthesis of 7-DHC, increasing the 7-DHC titer to 312.4 mg/L. Next, enzymes were compartmentalized into the endoplasmic reticulum (ER) and the ER lumen was enlarged by overexpressing INO2. The 7-DHC titer of the finally engineered yeast reached 455.6 mg/L in a shake flask and 2870 mg/L in a 5 L bioreactor, the highest 7-DHC titer reported so far. Overall, this study achieved a highly efficient 7-DHC synthesis by remodeling the complicated sterol synthesis modules, paving the way for large-scale 7-DHC bioprodn. in the future.

Bioresource Technology published new progress about 434-16-2. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Category: alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Radicioni, Milko; Caverzasio, Carol; Rovati, Stefano; Giori, Andrea Maria; Cupone, Irma; Marra, Fabio; Mautone, Giuseppe published the artcile< Comparative Bioavailability Study of a New Vitamin D3 Orodispersible Film Versus a Marketed Oral Solution in Healthy Volunteers>, HPLC of Formula: 434-16-2, the main research area is vitamin D3 bioavailability orodispersible orally disintegrating film immune system.

An orally disintegrating film (ODF) formulation of vitamin D3 that dissolves rapidly in the mouth without drinking or chewing may be a worthwhile alternative to currently available drug products for therapeutic vitamin D supplementation. This study aimed to compare the bioavailability of a single dose of a vitamin D3 25000 I. U. ODF with those of a marketed oral vitamin D3 preparation in healthy subjects. This Phase 1, randomised, parallel-group, open-label study compared the pharmacokinetics of calcifediol [25(OH)D3], the precursor of bioactive vitamin D3, after a single dose of a new vitamin D3 25,000 I. U. ODF with those of a Reference formulation (vitamin D3 25000 I.U./2.5 mL oral solution) in healthy adult subjects using a validated liquid chromatog.-tandem mass spectrometry (LC-MS/MS) assay. The primary objective was bioavailability under fed conditions, defined as maximum plasma concentration (Cmax) of 25(OH)D3 and area under the concentration-time curve from time zero to time t, the last quantifiable concentration (AUC0-t). The pharmacokinetics of 25(OH)D3 were also evaluated following the ODF administration under fasting conditions. Subjects were randomised to receive a single dose of the vitamin D3 25000 I. U. ODF or the Reference oral solution under fed conditions or the vitamin D3 ODF under fasting conditions. Forty-eight healthy subjects were randomised and completed the study. Overall, the pharmacokinetic profile was very similar across the three treatment groups, and bioavailability did not significantly differ among treatments. Under fed conditions, mean 25(OH)D3 plasma values for Cmax were 6.68 ± 2.03 vs. 6.61 ± 2.62 ng/mL for the Test vs. Reference formulations. Corresponding values for AUC0-t were 2364.80 ± 1336.97 vs. 2150.52 ± 1622.76 ng/mL x h. Mean Cmax was slightly lower (6.68 ± 2.03 vs 7.23 ± 1.48 ng/mL) and the time to reach peak concentration was delayed (144 h 36-312 vs. 42 h 2-480) with the ODF under fed vs. fasting conditions (p = 0.0371). The point estimates and 90% CIs of the Testfed/Referencefed ratios of the geometric means showed that the bioavailability of exogenous 25(OH)D3 was, both in rate and extent of absorption, slightly higher with the vitamin D3 ODF than the vitamin D3 oral solution under the administration conditions recommended for the vitamin D3 oral solution Palatability and ease of use of the ODF were satisfactory. Conclusion: The new ODF 25000 I. U. formulation provided a valuable alternative to the marketed oral solution for therapeutic vitamin D supplementation, with a bioavailability that was slightly higher than that of the vitamin D3 oral solution administered under the same conditions.

Clinical Drug Investigation published new progress about Bioavailability. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, HPLC of Formula: 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Ghersi, Dario; Genaro-Mattos, Thiago C. published the artcile< Identifying Molecular Fragments That Drive 7-Dehydrocholesterol Elevation>, Quality Control of 434-16-2, the main research area is cholesterol metabolism 7 dehydrocholesterol pharmacophore molBLOCKS DHCR7; Smith Lemli Opitz Syndrome.

Medications having the unwanted side effect of inhibiting 7-dehydrocholesterol reductase (DHCR7), one of the last enzymes in the cholesterol biosynthesis pathway, account for about 300 million yearly prescriptions in the United States. Many of these drugs are currently prescribed to pregnant women. Many DHCR7-inhibiting medications share chem. similarities, which can be the active substructure responsible for the medication affinity to the enzyme. This work highlights a computational strategy to identify enriched fragments in a set of DHCR7-inhibiting medications. The computational approach used here involves systematic fragmentation of mols. using the molBLOCKS tool, followed by enrichment anal. The results of this approach highlight putative pharmacophores that might be responsible for the DHCR7-inhibiting activity of some of these medications. The identification of DHCR7-inhibiting substructures is an important step toward knowledge-based drug development and can improve the neurodevelopmental safety of medications.

ACS Pharmacology & Translational Science published new progress about Chemoinformatics. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Quality Control of 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Kiourtzidis, Mikis; Kuehn, Julia; Brandsch, Corinna; Stangl, Gabriele I. published the artcile< Vitamin d status of mice deficient in scavenger receptor class B Type 1, cluster determinant 36 and ATP-binding cassette proteins G5/G8>, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is kidney liver heart vitamin D Srb1 Cd36 Abcg5; ATP-binding cassette transporters G5/G8; cluster determinant 36; mice; scavenger receptor class B type 1; vitamin D.

Classical lipid transporters are suggested to modulate cellular vitamin D uptake. This study investigated the vitamin D levels in serum and tissues of mice deficient in SR-B1 (Srb1-/-), CD36 (Cd36-/-) and ABC-G5/G8 (Abcg5/g8-/-) and compared them with corresponding wild-type (WT) mice. All mice received triple-deuterated vitamin D3 (vitamin D3-d3) for six weeks. All knockout mice vs. WT mice showed specific alterations in their vitamin D concentrations Srb1-/- mice had higher levels of vitamin D3-d3 in the serum, adipose tissue, kidney and heart, whereas liver levels of vitamin D3-d3 remained unaffected. Addnl., Srb1-/- mice had lower levels of deuterated 25-hydroxyvitamin D3 (25(OH)D3-d3) in the serum, liver and kidney compared to WT mice. In contrast, Cd36-/- and WT mice did not differ in the serum and tissue levels of vitamin D3-d3, but Cd36-/- vs. WT mice were characterized by lower levels of 25(OH)D3-d3 in the serum, liver and kidney. Finally, Abcg5/g8-/- mice tended to have higher levels of vitamin D3-d3 in the serum and liver. Major alterations in Abcg5/g8-/- mice were notably higher levels of 25(OH)D3-d3 in the serum and kidney, accompanied by a higher hepatic mRNA abundance of Cyp27a1 hydroxylase. To conclude, the current data emphasize the significant role of lipid transporters in the uptake, tissue distribution and activation of vitamin D.

Nutrients published new progress about Adipose tissue. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Recommanded Product: (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Wu, Xu; Pan, Xiaoli; Cao, Sumei; Xu, Faqiong; Lan, Liming; Zhang, Yingyan; Lian, Senyang; Yan, Meijiao; Li, Ang published the artcile< iTRAQ-based quantitative proteomic analysis provides insights into strong broodiness in Muscovy duck (Cairina moschata) combined with metabolomics analysis>, Formula: C27H44O, the main research area is proteome metabolome APOV1 SAA VLDLR Cairina; Broodiness; Metabolomics; Muscovy duck; Ovary; Proteomics; iTRAQ.

Much attention has been paid to the broodiness of the Muscovy duck, but the mol. mechanism of broodiness remains largely unknown. In this study, the ovary tissues of Muscovy ducks during the broody and laying periods were used to investigate differentially expressed proteins (DEPs) by the iTRAQ-based proteomics approach. A total of 335 DEPs were identified, including 139 up-regulated and 196 down-regulated proteins. Six proteins (APOV1, GAL, SAA, GNB5, VLDLR and CDK1) with higher changes in expression were selected, and these proteins are mainly involved in the pathways related to reproductive performance, such as Oocyte meiosis, and PI3K-Akt signaling pathway. Steroid biosynthesis was the most significantly enriched pathway by KEGG pathway enriched anal. The qRT-PCR anal. was applied to verify the proteomic anal. Meanwhile, metabolomics anal. found that several important differentially expressed metabolites (DEMs) (7-dehydrodesmosterol, 25-Hydroxyvitamin D3, 7-Dehydrocholesterol, Pregnanolone, Allopregnanolone and estrogen) that were also mainly involved in Steroid biosynthesis, Steroid hormone biosynthesis and Metabolic pathways. Crucially, the changes in the abundance of these metabolites are closely related to the changes in the protein abundance of proteins identified in the same pathway, and it is always the upstream key enzymes that influence the production of downstream metabolites.

Journal of Proteomics published new progress about Cairina moschata Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Formula: C27H44O.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Herron, Josi M.; Tomita, Hideaki; White, Collin C.; Kavanagh, Terrance J.; Xu, Libin published the artcile< Benzalkonium Chloride Disinfectants Induce Apoptosis, Inhibit Proliferation, and Activate the Integrated Stress Response in a 3-D in Vitro Model of Neurodevelopment>, SDS of cas: 434-16-2, the main research area is benzalkonium chloride neural stem cell neurosphere apoptosis proliferation stress.

We previously found that the widely used disinfectants, benzalkonium chlorides (BACs), alter cholesterol and lipid homeostasis in neuronal cell lines and in neonatal mouse brains. Here, we investigate the effects of BACs on neurospheres, an in vitro three-dimensional model of neurodevelopment. Neurospheres cultured from mouse embryonic neural progenitor cells (NPCs) were exposed to increasing concentrations (from 1 to 100 nM) of a short-chain BAC (BAC C12), a long-chain BAC (BAC C16), and AY9944 (a known DHCR7 inhibitor). We found that the sizes of neurospheres were decreased by both BACs but not by AY9944. Furthermore, we observed potent inhibition of cholesterol biosynthesis at the step of DHCR7 by BAC C12 but not by BAC C16, suggesting that cholesterol biosynthesis inhibition is not responsible for the observed reduction in neurosphere growth. By using immunostaining and cell cycle anal., we found that both BACs induced apoptosis and decreased proliferation of NPCs. To explore the mechanisms underlying their effect on neurosphere growth, we carried out RNA sequencing on neurospheres exposed to each BAC at 50 nM for 24 h, which revealed the activation of the integrated stress response by both BACs. Overall, these results suggest that BACs affect neurodevelopment by inducing the integrated stress response in a manner independent of their effects on cholesterol biosynthesis.

Chemical Research in Toxicology published new progress about Apoptosis. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, SDS of cas: 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts