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https://www.readbyqxmd.com/read/29783097/regulation-of-phytosterol-biosynthetic-pathway-during-drought-stress-in-rice
#1
M S Sujith Kumar, Ibandalin Mawlong, Kishwar Ali, Aruna Tyagi
Plants respond to drought stress in the form of various physio-biochemical and molecular changes at both cellular and molecular levels. Drought stress causes the destruction of cell membranes by disintegration of membrane lipids. One of the major groups of membrane lipids that plays important role in preserving the integrity of cell membranes is phytosterols. HMG-CoA reductase (HMGR) is the principal enzyme in the biosynthesis of plant sterols, synthesized via mevalonic acid pathway. Phospholipid: sterol acyltransferase (PSAT) is another important enzyme that plays an important role in turnover of phytosterols into steryl esters and helps maintain homeostasis of membrane lipids...
May 15, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29778238/interplay-between-estrogen-related-receptors-and-steroidogenesis-controlling-molecules-in-adrenals-in-vivo-and-in-vitro-study
#2
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29777848/effects-on-mortality-and-cardiovascular-events-of-adherence-to-guideline-recommended-therapy-4-years-after-lower-extremity-arterial-revascularization
#3
M Thiney, N Della Schiava, R Ecochard, P Feugier, P Lermusiaux, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme inhibitors (ACE) or Angiotensin receptor blockers (ARB), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk for cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events and additional vascular surgery in vascularized LE-PAD patients...
May 16, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29769046/%C3%AE-tocotrienol-induces-apoptosis-in-pancreatic-cancer-cells-by-upregulation-of-ceramide-synthesis-and-modulation-of-sphingolipid-transport
#4
Victoria E Palau, Kanishka Chakraborty, Daniel Wann, Janet Lightner, Keely Hilton, Marianne Brannon, William Stone, Koyamangalath Krishnan
BACKGROUND: Ceramide synthesis and metabolism is a promising target in cancer drug development. γ-tocotrienol (GT3), a member of the vitamin E family, orchestrates multiple effects that ensure the induction of apoptosis in both, wild-type and RAS-mutated pancreatic cancer cells. Here, we investigated whether these effects involve changes in ceramide synthesis and transport. METHODS: The effects of GT3 on the synthesis of ceramide via the de novo pathway, and the hydrolysis of sphingomyelin were analyzed by the expression levels of the enzymes serine palmitoyl transferase, ceramide synthase-6, and dihydroceramide desaturase, and acid sphingomyelinase in wild-type RAS BxPC3, and RAS-mutated MIA PaCa-2 and Panc 1 pancreatic cancer cells...
May 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29763460/lipophilic-statins-limit-cancer-cell-growth-and-survival-via-involvement-of-akt-signaling
#5
Colin H Beckwitt, Keisuke Shiraha, Alan Wells
The HMG-CoA reductase inhibitors, statins, have been used as lipid lowering drugs for decades and several epidemiological studies suggest statin usage correlates with a decreased incidence of cancer specific mortality in patients. However, the mechanism of this mortality benefit remains unclear. Here, we demonstrate that statin drug lipophilicity and affinity for its target enzyme, HMGCR, determine their growth suppressive potency against various tumor cell lines. The lipophilic atorvastatin decreases cancer cell proliferation and survival in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29761837/augmentation-of-the-cytotoxic-effects-of-nitrogen-containing-bisphosphonates-in-hypoxia
#6
Tetsuya Minegaki, Saya Koiki, Yutaro Douke, Chihiro Yamane, Ai Suzuki, Misato Mori, Masayuki Tsujimoto, Kohshi Nishiguchi
OBJECTIVES: Tumour hypoxia is a major obstacle in cancer therapy that leads to poor prognosis. Therefore, the development of cancer treatments that are effective in hypoxia is necessary. Nitrogen-containing bisphosphonates (N-BPs), which are used to treat bone disease, are cytotoxic to several cancer cells in normoxia. Therefore, we investigated the cytotoxicity of N-BPs in cancer cells in hypoxia. METHODS: We studied the cytotoxicities of N-BPs, statins and anticancer drugs in human cancer cells under hypoxic conditions (1% O2 )...
May 15, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29746786/vitamin-e-and-its-anticancer-effects
#7
Annette Abraham, Ajoe John Kattoor, Tom Saldeen, Jawahar L Mehta
Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, α, β, δ, γ isoforms of tocopherol and α, β, δ, γ isoforms of tocotrienol. Many studies have been performed to elucidate its role in cancer. Until last decade, major focus was on alpha tocopherol and its anticancer effects. However, major clinical trials using alpha-tocopherol like SELECT trial and ATBC trial did not yield meaningful results. Hence there was a shift of focus to gamma-tocopherol, delta-tocopherol and tocotrienol...
May 10, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29744294/synergistic-effects-of-hmg-coa-reductase-inhibitor-and-angiotensin-ii-receptor-blocker-on-load-induced-heart-failure
#8
Yusuke Ito, Yasuhiro Maejima, Natsuko Tamura, Yuka Shiheido-Watanabe, Masanori Konishi, Takashi Ashikaga, Kenzo Hirao, Mitsuaki Isobe
5-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have beneficial effects in patients with heart failure (HF), regardless of serum cholesterol levels. However, their synergic effects with angiotensin II receptor blocker (ARB) remain to be established. We assessed the existence and potential underlying mechanisms of the effects of combined ARB [losartan (LOS)] and statin [simvastatin (SIM)] on cardiac function in rats and mice with load-induced HF. Salt-loaded Dahl salt-sensitive (DS) rats were treated with vehicle, LOS, SIM, or LOS + SIM for 8 weeks...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29741465/preparation-of-biocompatible-copolymeric-micelles-as-a-carrier-of-atorvastatin-and-rosuvastatin-for-potential-anticancer-activity-study
#9
Manjili Hamidreza Kheiri, Niusha Alimohammadi, Hossein Danafar
Statins are widely used for the treatment of hypercholesterolemia. However, their inhibitory action on HMG-CoA reductase also results in the depletion of intermediate biosynthetic products, which importantly contribute to cell proliferation. The aim of the present study was to compare the effects of the individual commercially available statins on investigational breast cancer. Thus, in this study, biodegradable polymeric micelles as carrier of statins were prepared using biodegradable copolymers (PCL-PEG-PCL)...
May 9, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29738536/statins-impact-primary-embryonic-mouse-neural-stem-cell-survival-cell-death-and-fate-through-distinct-mechanisms
#10
Ross A Carson, Anthony C Rudine, Serena J Tally, Alexis L Franks, Krystle A Frahm, Jacob K Waldman, Neerupma Silswal, Suban Burale, James V Phan, Uma R Chandran, A Paula Monaghan, Donald B DeFranco
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway (CBP), and are used for the prevention of cardiovascular disease. The anti-inflammatory effects of statins may also provide therapeutic benefits and have led to their use in clinical trials for preeclampsia, a pregnancy-associated inflammatory condition, despite their current classification as category X (i.e. contraindicated during pregnancy). In the developing neocortex, products of the CBP play essential roles in proliferation and differentiation of neural stem-progenitor cells (NSPCs)...
2018: PloS One
https://www.readbyqxmd.com/read/29731020/the-genetic-link-between-diabetes-and-atherosclerosis
#11
REVIEW
Stephanie Ross, Hertzel Gerstein, Guillaume Paré
Epidemiological studies have indicated that the risk of atherothrombotic coronary artery disease (CAD) is higher in patients with diabetes, but these results have not been consistently observed across clinical trials. To address this apparent discrepancy, we can apply the results of genome-wide association studies (GWAS) to provide a better understanding of the shared genetic architecture of diabetes and atherothrombotic CAD. For instance, a large GWAS has identified 16 novel loci that are associated with both diabetes and atherothrombotic CAD...
May 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29724010/water-soluble-fish-protein-intake-led-to-lower-serum-and-liver-cholesterol-concentrations-in-obese-zucker-fa-fa-rats
#12
Aslaug Drotningsvik, Linn Anja Vikøren, Svein Are Mjøs, Åge Oterhals, Daniela Pampanin, Ola Flesland, Oddrun Anita Gudbrandsen
Proteins from different fish species and different raw materials such as fish fillets and by-products have shown promising cardioprotective effects in rodents and humans, including effects on cholesterol metabolism. Blue whiting is used mainly to produce fish meal for the feed industry and during this production, a water-soluble protein fraction, containing small peptides that are easily absorbed and may hold bioactive properties, is isolated. The effects of water-soluble fish protein on cholesterol metabolism were investigated in twelve male obese Zucker fa/fa rats...
May 1, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29720560/targeting-the-mevalonate-pathway-suppresses-vhl-deficient-cc-rcc-through-a-hif-dependent-mechanism
#13
Jordan M Thompson, Alejandro Alvarez, Monika K Singha, Matthew W Pavesic, Quy H Nguyen, Luke J Nelson, David A Fruman, Olga V Razorenova
Clear Cell Renal Cell Carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advance stages. The objective of this study was to investigate HMG-CoA Reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins...
May 2, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29717672/antiatherogenic-potential-of-extracts-from-the-gray-oyster-medicinal-mushroom-pleurotus-pulmonarius-agaricomycetes-in-vitro
#14
Mohamad Hamdi Zainal Abidin, Noorlidah Abdullah, Nurhayati Zainal Abidin
This study evaluates the in vitro inhibition of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) by Pleurotus pulmonarius extracts. The protective effect on the endothelial membrane against oxidative stress through the protection of nitric oxide bioavailability, as well as inhibition of endocan expression, was evaluated using human aortic endothelial cells (HAECs). Crude cold aqueous extract exhibited the most potent inhibitory activities against ACE and HMG-CoA reductase, with 61...
2018: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29707830/esrd-induced-dyslipidemia-should-management-of-lipid-disorders-differ-in-dialysis-patients
#15
Hamid Moradi, Elani Streja, Nosratola D Vaziri
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Although numerous modifiable risk factors in the pathogenesis of CVD and its associated mortality have been identified, dyslipidemia remains to be a key focus for therapy. In this regard, significant progress has been made in reducing cardiovascular mortality via the use of lipid-lowering agents such as HMG CoA reductase inhibitors (statins). Yet, despite the disproportionate risk of CVD and mortality in patients with advanced chronic and end stage renal disease (ESRD), treatment of dyslipidemia in this patient population has not been associated with a notable improvement in outcomes...
April 29, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29703846/-lpa-variants-are-associated-with-residual-cardiovascular-risk-in-patients-receiving-statins
#16
Wei-Qi Wei, Xiaohui Li, Qiping Feng, Michiaki Kubo, Iftikhar J Kullo, Peggy L Peissig, Elizabeth W Karlson, Gail P Jarvik, Ming Ta Michael Lee, Ning Shang, Eric A Larson, Todd Edwards, Christian Shaffer, Jonathan D Mosley, Shiro Maeda, Momoko Horikoshi, Marylyn Ritchie, Marc S Williams, Eric B Larson, David R Crosslin, Sarah T Bland, Jennifer A Pacheco, Laura J Rasmussen-Torvik, David Cronkite, George Hripcsak, Nancy J Cox, Russell A Wilke, C Michael Stein, Jerome I Rotter, Yukihide Momozawa, Dan M Roden, Ronald M Krauss, Joshua C Denny
Background -Coronary heart disease (CHD) is a leading cause of death globally. Although therapy with HMG-CoA reductase inhibitors (statins) decreases circulating levels of low-density lipoprotein cholesterol (LDL-C) and the incidence of CHD, additional events occur despite statin therapy in some individuals. The genetic determinants of this residual cardiovascular risk remain unknown. Methods -We performed a two-stage genome-wide association study (GWAS) of CHD events during statin therapy. We first identified 3,099 cases who experienced CHD events (defined as acute myocardial infarction or the need for coronary revascularization) during statin therapy and 7,681 controls without CHD events during comparable intensity and duration of statin therapy from four sites in the Electronic Medical Records and Genomics (eMERGE) Network...
April 27, 2018: Circulation
https://www.readbyqxmd.com/read/29702476/effect-of-lemongrass-water-extract-supplementation-on-atherogenic-index-and-antioxidant-status-in-rats
#17
Nuntiya Somparn, Suphaket Saenthaweeuk, Jarinyaporn Naowaboot, Atcharaporn Thaeomor, Veerapol Kukongviriyapan
Cymbopogon citratus (DC) Stapf., commonly known as lemongrass, possesses strong antioxidant and cardiotonic properties. Lemongrass water extract contains several polyphenolic compounds including gallic acid, isoquercetin, quercetin, rutin, catechin and tannic acid. Rutin, isoquercetin catechin and quercetin are the flavonoids most abundantly found in the extract. The extract significantly decreased total cholesterol, low-density lipoprotein and atherogenic index in rats after treatment (p < 0.05). Expression of genes and protein of sterol regulatory element binding protein-1c (SREBP1c) and HMG-CoA reductase (HMGR) was also lowered significantly in treated groups (p < 0...
June 1, 2018: Acta Pharmaceutica
https://www.readbyqxmd.com/read/29701171/risk-factors-for-rhabdomyolysis-with-hmg-coa-reductase-inhibitors-identified-using-a-postmarketing-surveillance-database-in-japan
#18
Masayuki Hashiguchi, Jun Hakamata, Mikiko Shimizu, Junya Maruyama, Tsuyoshi Shiga, Mayumi Mochizuki
OBJECTIVE: To investigate quantitatively the risk factors for rhabdomyolysis or related symptoms associated with HMG-CoA reductase inhibitors (statins), we used the lipid-lowering drug database (32,157 patients) developed by the RAD-AR Council, Japan, based on the postmarketing surveillance (PMS) data of pharmaceutical companies to perform a nested case-control study. MATERIALS AND METHODS: Of 26,849 patients taking statins, the case group was composed of 51 patients who experienced rhabdomyolysis or related symptoms while taking statins, and the control group was 1,020 patients randomly selected from patients who did not experience rhabdomyolysis or related symptoms while taking statins...
April 27, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29691631/lovastatin-synergizes-with-itraconazole-against-planktonic-cells-and-biofilms-of-candida-albicans-through-the-regulation-on-ergosterol-biosynthesis-pathway
#19
Yujie Zhou, Hong Yang, Xuedong Zhou, Hongke Luo, Fan Tang, Jin Yang, Gil Alterovitz, Lei Cheng, Biao Ren
The increase of fungal infectious diseases and lack of safe and efficacious antifungal drugs result in the urgent need of new therapeutic strategies. Here, we repurposed the lovastatin (LOV) as a synergistic antifungal potentiator to itraconazole (ITZ) against Candida albicans planktonic cells and biofilms in vitro for the first time. Mutants from ergosterol biosynthesis pathway were employed and key gene expression profiles of ergosterol pathway were also measured. LOV single treatment was unable to inhibit C...
April 25, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29691272/immune-mediated-necrotising-myopathy-a-rare-cause-of-hyperckaemia
#20
Emily Liang, Mandana Rastegar
Immune-mediated necrotising myopathy (IMNM) is a type of inflammatory myopathy characterised by acute or subacute severe proximal muscle weakness, significantly elevated creatine kinase levels, and prominent myofibre necrosis and regeneration with little or no inflammation. A subtype of IMNM identified by anti-HMG-CoA reductase (HMGCR)antibodies has been shown to be associated with statin exposure. Treatment of IMNM consists of immunosuppression with steroids, steroid-sparing agents, intravenous immune globulin and/or biologics...
April 24, 2018: BMJ Case Reports
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