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https://www.readbyqxmd.com/read/28826913/vorinostat-and-simvastatin-have-synergistic-effects-on-triple-negative-breast-cancer-cells-via-abrogating-rab7-prenylation
#1
Xinhui Kou, Yonghua Yang, Xiaoxiao Jiang, Huijuan Liu, Fanghui Sun, Xuan Wang, Longkai Liu, Hongrui Liu, Zhaohu Lin, Lan Jiang
Since the lack of targeted treatment, triple-negative breast cancer (TNBC) has poor outcomes. Histone deacetylase inhibitors (HDACi) blocking the activity of specific HDACs have emerged as cancer therapeutic agents. However, the therapeutic efficiency is still not satisfactory for patients with solid tumor. We thus performed screening for the synergistic agents of Vorinostat (SAHA). The resulting candidate Simvastatin was obtained. The efficacy and mechanism of combination have been studied in TNBC cells. The synergism of SAHA and Simvastatin was evaluated by IC50 of proliferation and combination index (CI)...
August 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28826810/precise-control-of-lycopene-production-to-enable-a-fast-responding-minimal-equipment-biosensor
#2
Monica P McNerney, Mark P Styczynski
Pigmented metabolites have great potential for use in biosensors that target low-resource areas, since sensor output can be interpreted without any equipment. However, full repression of pigment production when undesired is challenging, as even small amounts of enzyme can catalyze the production of large, visible amounts of pigment. The red pigment lycopene could be particularly useful because of its position in the multi-pigment carotenoid pathway, but commonly used inducible promoter systems cannot repress lycopene production...
August 4, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28826774/advances-in-basic-and-clinical-immunology-2016
#3
Javier Chinen, Yousef Badran, Raif S Geha, Janet S Chou, Ari J Fried
Advances in basic immunology in 2016 included studies that further characterized the role of different proteins in the differentiation of effector T cells and B cells, including cytokines and proteins involved in actin cytoskeleton. The regulation of granule formation and secretion in cytotoxic cells was also further described by examining patients with familial hemophagocytic lymphohystiocytosis. The role of prenylation in mevalonate kinase deficiency leading to inflammation has been established. We reviewed advances in clinical immunology as well as new approaches of whole genome sequencing and genes newly reported to be associated with immunodeficiency, such as linker of activation of T cells (LAT), B cell lymphoma 11B (BCL11B), RLTPR, moesin and JAK1...
August 18, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28813549/pcsk9-inhibitors-statins-low-density-lipoprotein-cholesterol-mevalonate-pathway-and-toxicity
#4
Carlos Guijarro
No abstract text is available yet for this article.
August 16, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28813546/pcsk9-inhibitors-statins-low-density-lipoprotein-cholesterol-mevalonate-pathway-and-toxicity-reply
#5
Michael J Koren, Marc S Sabatine
No abstract text is available yet for this article.
August 16, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28811511/from-metabolome-to-phenotype-gc-ms-metabolomics-of-developing-mutant-barley-seeds-reveals-effects-of-growth-temperature-and-genotype
#6
Bekzod Khakimov, Morten Arendt Rasmussen, Rubini Maya Kannangara, Birthe Møller Jespersen, Lars Munck, Søren Balling Engelsen
The development of crop varieties tolerant to growth temperature fluctuations and improved nutritional value is crucial due to climate change and global population growth. This study investigated the metabolite patterns of developing barley seed as a function of genotype and growth temperature for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#7
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808351/inhibition-of-the-mevalonate-pathway-augments-the-activity-of-pitavastatin-against-ovarian-cancer-cells
#8
Marwan Ibrahim Abdullah, Mohammed Najim Abed, Alan Richardson
Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC50 = 0.6-14 μM), zoledronic acid (IC50 = 21-57 μM), risedronate (IC50 > 100 μM) or GGTI-2133 (IC50 > 25 μM) inhibited the growth of ovarian cancer cell cultures...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28777842/-analysis-of-clinical-and-genetic-features-of-nine-patients-with-disseminated-superfacial-actinic-porokeratosis
#9
Xiuling Li, Qian Zhou, Lude Zhu, Zijun Zhao, Peiru Wang, Linglin Zhang, Guolong Zhang, Xiuli Wang
OBJECTIVE: To analyze the clinical and genetic features of 9 ethnic Han Chinese patients with disseminated superfacial actinic porokeratosis (DSAP). METHODS: Genomic DNA was extracted from peripheral blood samples collected from the patients. PCR and direct sequencing were carried out for five patients from a family, 4 sporadic cases, and 120 healthy controls to identify potential mutations of four genes (MVK, MVD, PMVK, FDPS) involved in the mevalonate pathway as well as SLC17A9, SSH1, and SART3 genes...
August 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28765914/atorvastatin-increases-fads1-fads2-and-elovl5-gene-expression-via-the-geranylgeranyl-pyrophosphate-dependent-rho-kinase-pathway-in-3t3-l1-cells
#10
Noriko Ishihara, Sawako Suzuki, Shou Tanaka, Yasuhiro Watanabe, Daiji Nagayama, Atsuhito Saiki, Tomoaki Tanaka, Ichiro Tatsuno
Numerous clinical studies have reported that statins increase the plasma concentration of arachidonic acid, which is an ω-6 long-chain polyunsaturated fatty acid (LCPUFA), and decrease the concentrations of eicosapentaenoic acid and docosahexaenoic acid, which are ω‑3 LCPUFAs. These findings indicate that statins may affect the endogenous synthesis of LCPUFAs, which is regulated by fatty acid desaturases (FADSs) and elongation of very long‑chain fatty acids proteins (ELOVLs). The present study aimed to investigate the roles of the intrinsic mevalonate cascade and Rho‑dependent pathway in statin‑induced regulation of these desaturases and elongases, as well as cell viability using mouse 3T3‑L1 cells...
August 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765912/disorder-of-the-mevalonate-pathway-inhibits-calcium-induced-differentiation-of-keratinocytes
#11
Rui Jin, Xin Luo, Kang Luan, Li Liu, Liang-Dan Sun, Sen Yang, Sheng-Quan Zhang, Xue-Jun Zhang
Mutation of genes encoding the enzymes of the mevalonate pathway cause a variety of diseases, including skin disorders. Mutation of four genes in this pathway, including mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase and farnesyl diphosphate synthase, have demonstrated to be responsible for porokeratosis (PK). However, the pathogenesis of PK remains unclear. In the present study, specific enzyme inhibitors of the mevalonate pathway, including pravastatin (PRA), alendronate (ALD), farnesyl transferase inhibitor (FTI‑277) and geranylgeranyl transferase inhibitor (GGTI‑298), were used to investigate the effect on differentiation of keratinocytes (KCs)...
August 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28762089/secondary-metabolites-from-higher-fungi
#12
He-Ping Chen, Ji-Kai Liu
Secondary metabolites of higher fungi (mushrooms) are an underexplored resource compared to plant-derived secondary metabolites. An increasing interest in mushroom natural products has been noted in recent years. This chapter gives a comprehensive overview of the secondary metabolites from higher fungi, with 765 references highlighting the isolation, structure elucidation, biological activities, chemical syntheses, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms. Mushroom toxins are also included in each section...
2017: Progress in the Chemistry of Organic Natural Products
https://www.readbyqxmd.com/read/28732362/acute-atorvastatin-treatment-restores-the-cardioprotective-effects-of-ischemic-postconditioning-in-hyperlipidemic-rats
#13
Tao Sun, Hong-Ju Zhang, Chayakrit Krittanawong, Su Wang, Ying Tao, Zhao Li, Qiancheng Yin, Donghua Zhang, Qian Wang, Ji Huang, Jingmei Zhang, Zhizhong Li, Yutong Cheng
BACKGROUND: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729418/myc-regulated-mevalonate-metabolism-maintains-brain-tumor-initiating-cells
#14
Xiuxing Wang, Zhi Huang, Qiulian Wu, Briana C Prager, Stephen C Mack, Kailin Yang, Leo J Y Kim, Ryan C Gimple, Yu Shi, Sisi Lai, Qi Xie, Tyler E Miller, Christopher G Hubert, Anne Song, Zhen Dong, Wenchao Zhou, Xiaoguang Fang, Zhe Zhu, Vaidehi Mahadev, Shideng Bao, Jeremy N Rich
Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wildtype IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor initiating cells (BTICs) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28710496/dietary-geranylgeraniol-can-limit-the-activity-of-pitavastatin-as-a-potential-treatment-for-drug-resistant-ovarian-cancer
#15
Elizabeth de Wolf, Marwan Ibrahim Abdullah, Stefanie M Jones, Karen Menezes, Darren M Moss, Falko P Drijfhout, Sarah R Hart, Clare Hoskins, Euan A Stronach, Alan Richardson
Pre-clinical and retrospective studies of patients using statins to reduce plasma cholesterol have suggested that statins may be useful to treat cancer. However, prospective clinical trials have yet to demonstrate significant efficacy. We have previously shown that this is in part because a hydrophobic statin with a long half-life is necessary. Pitavastatin, the only statin with this profile, has not undergone clinical evaluation in oncology. The target of pitavastatin, hydroxymethylglutarate coenzyme-A reductase (HMGCR), was found to be over-expressed in all ovarian cancer cell lines examined and upregulated by mutated TP53, a gene commonly altered in ovarian cancer...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709932/assessing-glycolytic-flux-alterations-resulting-from-genetic-perturbations-in-e-coli-using-a-biosensor
#16
Christina E Lehning, Solvej Siedler, Mostafa M H Ellabaan, Morten O A Sommer
We describe the development of an optimized glycolytic flux biosensor and its application in detecting altered flux in a production strain and in a mutant library. The glycolytic flux biosensor is based on the Cra-regulated ppsA promoter of E. coli controlling fluorescent protein synthesis. We validated the glycolytic flux dependency of the biosensor in a range of different carbon sources in six different E. coli strains and during mevalonate production. Furthermore, we studied the flux-altering effects of genome-wide single gene knock-outs in E...
July 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28706181/effects-of-an-enriched-extract-of-paeoniflorin-a-monoterpene-glycoside-used-in-chinese-herbal-medicine-on-cholesterol-metabolism-in-a-hyperlipidemic-rat-model
#17
Huiming Hu, Qiaoqiao Zhu, Jie Su, Yajun Wu, Yanchen Zhu, Yin Wang, Hui Fang, Minxia Pang, Bo Li, Suhong Chen, Guiyuan Lv
BACKGROUND Paeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model. MATERIAL AND METHODS Male Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR)...
July 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28698273/viral-micrornas-repress-the-cholesterol-pathway-and-25-hydroxycholesterol-inhibits-infection
#18
Anna K P Serquiña, Diane M Kambach, Ontara Sarker, Joseph M Ziegelbauer
From various screens, we found that Kaposi's sarcoma-associated herpesvirus (KSHV) viral microRNAs (miRNAs) target several enzymes in the mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate-limiting step in the mevalonate pathway]), and farnesyl-diphosphate farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient to reduce intracellular cholesterol levels; however, small interfering RNAs (siRNAs) targeting only HMGCS1 did not reduce cholesterol levels...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28685731/dermoscopic-features-and-gene-mutation-in-the-mevalonate-pathway-of-five-sporadic-patients-with-porokeratosis
#19
Rui-Feng Sun, Hui Chen, Wei Zhu, Shi Lian
No abstract text is available yet for this article.
July 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28684180/enhancing-linalool-production-by-engineering-oleaginous-yeast-yarrowia-lipolytica
#20
Xuan Cao, Liu-Jing Wei, Jia-Yu Lin, Qiang Hua
In this study, stepwise increases in linalool production were obtained by combining metabolic engineering and process optimization of an unconventional oleaginous yeast Yarrowia lipolytica. The linalool synthetic pathway was successfully constructed by heterologously expressing a codon-optimized linalool synthase gene from Actinidia arguta in Y. lipolytica. To enhance linalool productivity, key genes involved in the mevalonate pathway were overexpressed in different combinations. Moreover, the overexpression of mutant ERG20(F88W-N119W) gene resulted in further linalool production...
June 23, 2017: Bioresource Technology
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