Review
Chemistry, Medicinal
Tyler Bahr, Gavin Butler, Christian Rock, Kyle Welburn, Kathryn Allred, Damian Rodriguez
Summary: Mono- and sesquiterpenoids are the main chemical constituents of essential oils, which have lipid-lowering properties. Many essential oil compounds have similar effects on cholesterol metabolism, likely through direct agonism of peroxisome-proliferator-activated receptors and direct interaction with sterol-sensing domains. Terpene derivatives in essential oils may have cholesterol-lowering activity and could potentially synergize with statins, but further high-quality studies are needed to establish their clinical efficacy.
PHYTOTHERAPY RESEARCH
(2021)
Article
Microbiology
Cene Gostincar, Jason E. Stajich, Anja Kejzar, Sunita Sinha, Corey Nislow, Metka Lenassi, Nina Gunde-Cimerman
Summary: Experimental evolution of the extremely halotolerant black yeast Hortaea werneckii revealed changes in various aspects including cell wall and morphology, resistance, and genome during long-term growth under extreme salinity. This indicates that prolonged exposure to extreme salinity may lead to adjustments in cellular mechanisms and adaptations.
Review
Pharmacology & Pharmacy
David M. Dolivo, Charlotte R. Reed, Kristine A. Gargiulo, Adrian E. Rodrigues, Robert D. Galiano, Thomas A. Mustoe, Seok Jong Hong
Summary: Fibrosis is a common pathological repair process in organs, but there is a lack of effective therapeutic methods. Repurposing existing drugs, such as statins, can be a complementary strategy to treat tissue fibrosis. Statins have been found to have anti-fibrotic effects through various mechanisms, and a better understanding of these effects can aid in the development of novel therapeutic agents.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Janik, Urszula Perlinska-Lenart, Katarzyna Gawarecka, Justyna Augustyniak, Ewelina Bratek-Gerej, Przemyslaw Bernat, Sebastian Pilsyk, Patrycja Skalmowska, Grazyna Palamarczyk, Ewa Swiezewska, Joanna S. Kruszewska
Summary: Protein glycosylation requires dolichyl phosphate as a carbohydrate carrier. In Candida, the saturation of dolichols is catalyzed by polyprenyl reductase Dfg10 and some unknown enzymes. This study aimed to identify these enzymes in Candida. Two ORFs in Candida albicans were found to have a domain similar to the polyprenyl reductase and enoyl-transferase in Saccharomyces cerevisiae. Deletion of one of these ORFs impaired the saturation of dolichols, and limiting its expression reduced the cellular level of dolichols and polyprenols. This reduction was due to a lower expression of early-stage enzymes in the mevalonate pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Dongbo Yu, James K. Liao
Summary: This review discusses the development of statins, their non-lipid-lowering benefits, and proposes future research directions in this field.
CARDIOVASCULAR RESEARCH
(2022)
Article
Endocrinology & Metabolism
Man K. S. Lee, Olivia D. Cooney, Xuzhu Lin, Shaktypreya Nadarajah, Dragana Dragoljevic, Kevin Huynh, Danise-Ann Onda, Sandra Galic, Peter J. Meikle, Thomas Edlund, Morgan D. Fullerton, Bruce E. Kemp, Andrew J. Murphy, Kim Loh
Summary: The study revealed that the AMPK/HMGCR axis plays a crucial role in the development of atherosclerosis. Defects in AMPK regulation of HMGCR lead to increased aortic lesions, plaque-associated macrophages, lipid accumulation, and atherogenic monocytes.
MOLECULAR METABOLISM
(2022)
Article
Chemistry, Medicinal
Xing-Zi Li, Shi-You Jiang, Guo-Qiang Li, Qian-Ru Jiang, Jue-Wan Li, Chen-Chen Li, Yu-Qin Han, Bao-Liang Song, Xin-Ran Ma, Wei Qi, Wen-Wei Qiu
Summary: A series of novel HMG499 analogs were synthesized and one of the compounds, 29 (QH536), showed potent activity in promoting HMGCR degradation without inducing cholesterol accumulation in cells. Compound 29 also exhibited effects on lowering cholesterol levels and suppressing various related genes, making it a potential candidate for the treatment of CVD and NASH.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Je-Wen Liou, Hemalatha Mani, Jui-Hung Yen
Summary: Hepatitis is an inflammatory disease of the liver caused by viral infections, most commonly hepatitis B and hepatitis C. Host lipid metabolism, particularly cholesterol metabolism, is crucial for hepatitis viral infection and life cycle. Manipulating host cholesterol metabolism-related genes and proteins, such as using cholesterol-lowering drugs, has shown promising results in the treatment of viral hepatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jia-Li Feng, Suzanne C. Dixon-Suen, Susan J. Jordan, Penelope M. Webb
Summary: The use of statins may provide a survival benefit for women with ovarian cancer, particularly for those with endometrioid cancers. However, bias in observational studies poses challenges in conclusively establishing this association.
BRITISH JOURNAL OF CANCER
(2021)
Article
Dermatology
Sayaka Kuwatsuka, Yuta Koike, Yutaka Kuwatsuka, Toshifumi Yamaoka, Hiroyuki Murota
Summary: The study revealed that HMG-CoA reductase inhibitors impact epidermal homeostasis, with claudin-7 showing high expression in the keratohyalin granules of psoriatic lesions but not in normal epidermis.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2021)
Article
Agriculture, Dairy & Animal Science
Janaina S. da Silva, Alessandra F. Rosa, Cristina T. Moncau, Barbara Silva-Vignato, Silvana Marina P. Pugine, Mariza P. de Melo, Joao Marcelo D. Sanchez, Marcus Antonio Zanetti
Summary: The effects of different sources and concentrations of selenium on glutathione forms and cholesterol metabolism in beef cattle were investigated in this study. Selenium supplementation can impact cholesterol metabolism by affecting GSH/GSSG ratio, GSH-Px, and HMGCR. The interaction between selenium source and concentration can influence glutathione forms.
JOURNAL OF ANIMAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Shubhi Singh, Smriti Gaur
Summary: Hypercholesterolemia is a major health concern and research has shown that bioactive compounds from edible seeds have strong binding interactions with HMG-CoA reductase, a key protein in cholesterol metabolism. These compounds have favorable drug likeliness and ADME properties, with good absorption in the human intestine. Molecular dynamics simulation studies provide insights into the stability of these compounds under simulated conditions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Jiwon Hwang, Brian G. Peterson, Jeffrey Knupp, Ryan D. Baldridge
Summary: Misfolded proteins in the ER are removed through ERAD, a process involving membrane protein quality control. While ERAD is known to regulate lipid biosynthetic enzymes, the impact of lipid composition on ERAD is unknown. This study shows that specific ceramides in the ER membrane can affect ERAD function by impairing substrate extraction.
Article
Biochemistry & Molecular Biology
Maria Giovanna Lupo, Silvia Marchiano, Maria Pia Adorni, Francesca Zimetti, Massimiliano Ruscica, Maria Francesca Greco, Alberto Corsini, Nicola Ferri
Summary: Overexpression of PCSK9 in rat SMCs led to downregulation of LDL receptor and marker of contractile phenotype. This resulted in increased cell proliferation rate and partial resistance to simvastatin, indicating a potential role of PCSK9 in atherosclerotic plaque development and pharmacological response to statins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Verena Korte, Guenther Gademann, Ahmed Gawish, Hans-Joachim Ochel
Summary: This study investigated the antiproliferative effects of simvastatin in combination with ionizing radiation on prostate cancer cells, and found that radiation had a stronger inhibitory effect compared to simvastatin alone. However, the combined application of both modalities had a synergistic effect. Simvastatin exerted its antiproliferative effects by inducing the elevation of HMG-CoA reductase levels.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
