3,534 results match your criteria mevalonate pathway

Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty.

Curr Res Toxicol 2020 Jun 27;1:149-160. Epub 2020 Nov 27.

Department of Structural and Functional Biology, São Paulo State University (Unesp), Institute of Biosciences, Botucatu, SP, Brazil.

Statins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by "pleiotropic effects", related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Read More

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Exometabolome profiling reveals activation of the carnitine buffering pathway in fed-batch cultures of CHO cells co-fed with glucose and lactic acid.

Biotechnol Prog 2021 Jul 30. Epub 2021 Jul 30.

Microbial & Cell Culture Development, GlaxoSmithKline R&D, King of Prussia, PA, USA.

Adjustments to CHO cell physiology were recently observed during implementation of a Raman spectroscopy-based glucose and lactate control strategy . To further understand how these cells, under monoclonal antibody (mAb) production conditions, utilized the extra lactic acid fed, we performed a comprehensive semi-quantitative and time-dependent analysis of the exometabolome. This study focused on the CHO cell's metabolic shift from the fifth day of culture. Read More

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Pitavastatin stimulates retinal angiogenesis via HMG-CoA reductase-independent activation of RhoA-mediated pathways and focal adhesion.

Graefes Arch Clin Exp Ophthalmol 2021 Jul 30. Epub 2021 Jul 30.

Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.

Background: Excessive angiogenesis of the retina is a key component of irreversible causes of blindness in many ocular diseases. Pitavastatin is a cholesterol-lowering drug used to reduce the risk of cardiovascular diseases. Various studies have shown the effects of pitavastatin on angiogenesis but the conclusions are contradictory. Read More

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Metabolic engineering of for terpenoids production: advances and perspectives.

Crit Rev Biotechnol 2021 Jul 29:1-16. Epub 2021 Jul 29.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

Terpenoids are a large family of natural products with diversified structures and functions that are widely used in the food, pharmaceutical, cosmetic, and agricultural fields. However, the traditional methods of terpenoids production such as plant extraction and chemical synthesis are inefficient due to the complex processes, high energy consumption, and low yields. With progress in metabolic engineering and synthetic biology, microbial cell factories provide an interesting alternative for the sustainable production of terpenoids. Read More

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Carboxylesterases for the hydrolysis of acetoacetate esters and their applications in terpenoid production using Escherichia coli.

Appl Microbiol Biotechnol 2021 Jul 29. Epub 2021 Jul 29.

Department of Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyamacho-Minami, Tottori, 680-8552, Japan.

Pathway engineering is a useful technology for producing desired compounds on a large scale by modifying the biosynthetic pathways of host organisms using genetic engineering. We focused on acetoacetate esters as novel low-cost substrates and established an efficient terpenoid production system using pathway-engineered recombinant Escherichia coli. Functional analysis using recombinant E. Read More

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Comparative transcriptome analysis reveals sesquiterpenoid biosynthesis among 1-, 2- and 3-year old Atractylodes chinensis.

BMC Plant Biol 2021 Jul 27;21(1):354. Epub 2021 Jul 27.

Hebei Key Laboratory of Crop Stress Biology (in Preparation), Hebei Normal University of Science & Technology, Qinhuangdao, 066004, Hebei, China.

Background: Atractylodes chinensis (DC.) Koidz is a well-known medicinal plant containing the major bioactive compound, atractylodin, a sesquiterpenoid. High-performance liquid chromatography (HPLC) analysis demonstrated that atractylodin was most abundant in 3-year old A. Read More

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Statins: a repurposed drug to fight cancer.

J Exp Clin Cancer Res 2021 Jul 24;40(1):241. Epub 2021 Jul 24.

Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, 230001, P. R. China.

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. Read More

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Syntrophic co-culture of a methanotroph and heterotroph for the efficient conversion of methane to mevalonate.

Metab Eng 2021 Jul 20;67:285-292. Epub 2021 Jul 20.

Synthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea; Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science & Technology (UST), Daejeon, 34113, Republic of Korea. Electronic address:

As the bioconversion of methane becomes increasingly important for bio-industrial and environmental applications, methanotrophs have received much attention for their ability to convert methane under ambient conditions. This includes the extensive reporting of methanotroph engineering for the conversion of methane to biochemicals. To further increase methane usability, we demonstrated a highly flexible and efficient modular approach based on a synthetic consortium of methanotrophs and heterotrophs mimicking the natural methane ecosystem to produce mevalonate (MVA) from methane. Read More

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(-)-α-Bisabolol Production in Engineered Expressing a Novel (-)-α-Bisabolol Synthase from the Globe Artichoke var. .

J Agric Food Chem 2021 Aug 20;69(30):8492-8503. Epub 2021 Jul 20.

Synthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.

(-)-α-Bisabolol is a functional ingredient in various health and cosmetic products and has antibacterial, anti-inflammatory, and wound healing properties. (-)-α-Bisabolol is chemically synthesized and produced by steam distillation of essential oils extracted from Brazilian Candeia (). To sustainably produce pure (-)-α-bisabolol, we previously engineered to produce 9. Read More

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Altered cholesterol homeostasis in critical illness-induced muscle weakness: effect of exogenous 3-hydroxybutyrate.

Crit Care 2021 07 17;25(1):252. Epub 2021 Jul 17.

Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49 bus 503, 3000, Leuven, Belgium.

Background: Muscle weakness is a complication of critical illness which hampers recovery. In critically ill mice, supplementation with the ketone body 3-hydroxybutyrate has been shown to improve muscle force and to normalize illness-induced hypocholesterolemia. We hypothesized that altered cholesterol homeostasis is involved in development of critical illness-induced muscle weakness and that this pathway can be affected by 3-hydroxybutyrate. Read More

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Cholesterol synthesis inhibition or depletion in axon regeneration.

Bor Luen Tang

Neural Regen Res 2022 Feb;17(2):271-276

Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.

Cholesterol is biosynthesized by all animal cells. Beyond its metabolic role in steroidogenesis, it is enriched in the plasma membrane where it has key structural and regulatory functions. Cholesterol is thus presumably important for post-injury axon regrowth, and this notion is supported by studies showing that impairment of local cholesterol reutilization impeded regeneration. Read More

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February 2022

Mevalonate blockade in cancer cells triggers CLEC9A+ dendritic cell-mediated antitumor immunity.

Cancer Res 2021 Jul 15. Epub 2021 Jul 15.

Experiment Medicine, Sun Yat-sen University Cancer Center

Hyperactive mevalonate (MVA) metabolic activity is often observed in cancer cells, and blockade of this pathway inhibits tumor cell lipid synthesis and cell growth and enhances tumor immunogenicity. How tumor cell MVA metabolic blockade promotes antitumor immune responses, however, remains unclear. Here we show that inhibition of the MVA metabolic pathway in tumor cells elicits type 1 classical dendritic cells (cDC1)-mediated tumor recognition and antigen cross-presentation for antitumor immunity. Read More

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Regulation of hepatic coenzyme Q biosynthesis by dietary omega-3 polyunsaturated fatty acids.

Redox Biol 2021 Jul 3;46:102061. Epub 2021 Jul 3.

Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario CeiA3, Córdoba, Spain. Electronic address:

Dietary fats are important for human health, yet it is not fully understood how different fats affect various health problems. Although polyunsaturated fatty acids (PUFAs) are generally considered as highly oxidizable, those of the n-3 series can ameliorate the risk of many age-related disorders. Coenzyme Q (CoQ) is both an essential component of the mitochondrial electron transport chain and the only lipid-soluble antioxidant that animal cells can synthesize. Read More

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Production of C20, C30 and C40 terpenes in the engineered phototrophic bacterium Rhodobacter capsulatus.

J Biotechnol 2021 Jul 5;338:20-30. Epub 2021 Jul 5.

Institute of Molecular Enzyme Technology, Heinrich Heine University Düsseldorf, Forschungszentrum Jülich, Jülich, Germany; Cluster of Excellence on Plant Sciences (CEPLAS), Germany; Bioeconomy Science Center (BioSC), Forschungszentrum Jülich, Jülich, Germany. Electronic address:

Terpenes constitute one of the largest groups of secondary metabolites that are used, for example, as food-additives, fragrances or pharmaceuticals. Due to the formation of an intracytoplasmic membrane system and an efficient intrinsic tetraterpene pathway, the phototrophic α-proteobacterium Rhodobacter capsulatus offers favorable properties for the production of hydrophobic terpenes. However, research efforts have largely focused on sesquiterpene production. Read More

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Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.

J Med Chem 2021 Jul 8;64(14):9677-9710. Epub 2021 Jul 8.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego Street 116, 90-924 Łódź, Poland.

A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein-protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Read More

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Cholesterol Paradigm and Beyond in Atherosclerotic Cardiovascular Disease: Cholesterol, Sterol regulatory element-binding Protein, Inflammation, and Vascular Cell Mobilization in Vasculopathy.

Cardiol Rev 2021 Jul 2. Epub 2021 Jul 2.

Division of Cardiology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA William H. Frishman, MD, Department of Medicine, New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY 10595. E-mail:

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). How cholesterol and its carrier lipoproteins are involved in ASCVD is still under extensive investigation. Satins are thus far the best proven class of cholesterol lowering medications to improve the clinical outcomes of ASCVD. Read More

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Manipulation of DXP pathway for andrographolide production in callus cultures of Andrographis paniculata.

Planta 2021 Jul 5;254(2):23. Epub 2021 Jul 5.

Plant Molecular Cytogenetics and Plant Biotechnology Laboratory, Department of Botany, Centre of Advanced Studies, University of Calcutta, Kolkata, West Bengal, 700019, India.

Main Conclusion: Greening of in vitro callus cultures and andrographolide over-accumulation was achieved by manipulating light exposure and media composition, when the biosynthetic cascade was channeled through the DXP pathway. Andrographolide, the primary biologically active compound of Andrographis paniculata, is produced through coordinated action of two pathways, the classical cytosolic mevalonate pathway and the alternative plastidial non-mevalonate pathway (Deoxy-xylulose Phosphate pathway). In vitro callus cultures of A. Read More

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Interdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity.

Cells 2021 Jun 29;10(7). Epub 2021 Jun 29.

Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany.

The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very‑low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. Read More

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Comparison of Transcriptomic Profiles of MiaPaCa-2 Pancreatic Cancer Cells Treated with Different Statins.

Molecules 2021 Jun 9;26(12). Epub 2021 Jun 9.

Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Špitálska 24, 813 72 Bratislava, Slovakia.

Statins have been widely used for the treatment of hypercholesterolemia due to their ability to inhibit HMG-CoA reductase, the rate-limiting enzyme of de novo cholesterol synthesis, via the so-called mevalonate pathway. However, their inhibitory action also causes depletion of downstream intermediates of the pathway, resulting in the pleiotropic effects of statins, including the beneficial impact in the treatment of cancer. In our study, we compared the effect of all eight existing statins on the expression of genes, the products of which are implicated in cancer inhibition and suggested the molecular mechanisms of their action in epigenetic and posttranslational regulation, and in cell-cycle arrest, death, migration, or invasion of the cancer cells. Read More

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Role of Withaferin A and Its Derivatives in the Management of Alzheimer's Disease: Recent Trends and Future Perspectives.

Molecules 2021 Jun 17;26(12). Epub 2021 Jun 17.

Department of Chemistry, The University of Jordan, Amman 11942, Jordan.

Globally, Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative disorders associated with cognitive decline and memory deficits due to beta-amyloid deposition (Aβ) and tau protein hyperphosphorylation. To date, approximately 47 million people worldwide have AD. This figure will rise to an estimated 75. Read More

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Chemistry, Pharmacology and Therapeutic Potential of Swertiamarin - A Promising Natural Lead for New Drug Discovery and Development.

Drug Des Devel Ther 2021 21;15:2721-2746. Epub 2021 Jun 21.

D.S.T.S. Mandal's College of Pharmacy, Solapur, Maharashtra, India.

Swertiamarin, a seco-iridoid glycoside, is mainly found in Blume () and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. Read More

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ATP Drives Efficient Terpene Biosynthesis in Marine Thraustochytrids.

mBio 2021 06 29;12(3):e0088121. Epub 2021 Jun 29.

Department of Microbiology, Miami University, Oxford, Ohio, USA.

Understanding carbon flux controlling mechanisms in a tangled metabolic network is an essential question of cell metabolism. Secondary metabolism, such as terpene biosynthesis, has evolved with low carbon flux due to inherent pathway constraints. Thraustochytrids are a group of heterotrophic marine unicellular protists and can accumulate terpenoids under the high-salt conditions in their natural environment. Read More

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Function of mevalonate pathway genes in the synthesis of frontalin in Chinese white pine beetle, Dendroctonus armandi (curculionidae: Scolytinae).

Arch Insect Biochem Physiol 2021 Aug 25;107(4):e21828. Epub 2021 Jun 25.

College of Forestry, Northwest A and F University, Yangling, Shaanxi, China.

The Chinese white pine beetle (Dendroctonus armandi Tsai and Li) is a significant pest of pine forests in the Qinling and Bashan Mountains of China. Adult males commonly produce frontalin using precursors synthesized through the mevalonate pathway, which is regulated by juvenile hormone III (JHIII). In this study, the expression levels of mevalonate pathway genes were quantified after phloem feeding and topical application of the JHIII solution. Read More

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Bisphosphonate Use Does Not Impact Survival in Patients with Pancreatic Cancer: A Propensity Score Matching Analysis.

Gut Liver 2021 Jun 25. Epub 2021 Jun 25.

Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Background/aims: : Bisphosphonates are increasingly recognized for their anti-neoplastic properties, which are the result of their action on the mevalonate pathway. Our primary aim was to investigate the association between bisphosphonate use and survival in patients with pancreatic cancer. Since statins also act on the mevalonate pathway, we also investigated the effect of the combined use of bisphosphonates and statins on survival. Read More

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Expressional diversity of grapevine 3-Hydroxy-3-methylglutaryl-CoA reductase (VvHMGR) in different grapes genotypes.

BMC Plant Biol 2021 Jun 19;21(1):279. Epub 2021 Jun 19.

College of Horticulture, Nanjing Agricultural University, Jiangsu Province, Nanjing City, 210095, PR China.

Background: 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a key enzyme in the mevalonate (MVA) pathway, which regulates the metabolism of terpenoids in the cytoplasm and determines the type and content of downstream terpenoid metabolites.

Results: Results showed that grapevine HMGR family has three members, such as VvHMGR1, VvHMGR2, and VvHMGR3. The expression of VvHMGRs in 'Kyoho' has tissue specificity, for example, VvHMGR1 keeps a higher expression, VvHMGR2 is the lowest, and VvHMGR3 gradually decreases as the fruit development. Read More

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A toxicological evaluation of geranylgeraniol.

Regul Toxicol Pharmacol 2021 Aug 16;124:104975. Epub 2021 Jun 16.

TOXI-COOP Zrt., Berlini Utca 47-49, H-1045, Budapest, Hungary. Electronic address:

Geranylgeraniol (GGOH) is an isoprenoid compound found in annatto seeds and an intermediate of the mevalonate pathway found within organisms serving various functions. Toxicological studies on its safety profile are not readily available. To assess the safety of GGOH, a molecularly distilled, food grade annatto oil, consisting of approximately 80% trans-GGOH, was subjected to a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test in order to investigate its genotoxic potential and a 90-day repeated-dose oral toxicity study in rats in order to investigate its potential subchronic toxicity and identify any target organs. Read More

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Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner.

J Gerontol A Biol Sci Med Sci 2021 Jun 17. Epub 2021 Jun 17.

Healthy Lifespan Institute, Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield.

Over recent decades, increased longevity has not been paralleled by extended healthspan, resulting in more years spent with multiple diseases in older age. As such, interventions to improve healthspan are urgently required. Zoledronate is a nitrogen containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase (FPPS) enzyme, central to the mevalonate pathway. Read More

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Increased accumulation of squalene in engineered through deletion of and .

Appl Environ Microbiol 2021 Jun 16:AEM0048121. Epub 2021 Jun 16.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.

Squalene is a triterpenoid serving as an ingredient of various products in the food, cosmetic, pharmaceutical industries. The oleaginous yeast offers enormous potential as a microbial chassis for the production of terpenoids, such as carotenoid, limonene, linalool, and farnesene as the yeast provides ample storage space for hydrophobic products. Here we present a metabolic design that allows the enhanced accumulation of squalene in . Read More

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Strategies for enhancing terpenoids accumulation in microalgae.

Appl Microbiol Biotechnol 2021 Jun 14;105(12):4919-4930. Epub 2021 Jun 14.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2 Xuelin Road, Qixia District, Nanjing, People's Republic of China.

Terpenoids represent one of the largest class of chemicals in nature, which play important roles in food and pharmaceutical fields due to diverse biological and pharmacological activities. Microorganisms are recognized as a promising source of terpenoids due to its short growth cycle and sustainability. Importantly, microalgae can fix inorganic carbon through photosynthesis for the growth of themselves and the biosynthesis of various terpenoids. Read More

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Geranylgeraniol prevents zoledronic acid-mediated reduction of viable mesenchymal stem cells via induction of Rho-dependent YAP activation.

R Soc Open Sci 2021 Jun 9;8(6):202066. Epub 2021 Jun 9.

Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, Pathumthani 12120, Thailand.

Long-term use of zoledronic acid (ZA) increases the risk of medication-related osteonecrosis of the jaw (MRONJ). This may be attributed to ZA-mediated reduction of viable mesenchymal stem cells (MSCs). ZA inhibits protein geranylgeranylation, thus suppressing cell viability and proliferation. Read More

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