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https://www.readbyqxmd.com/read/29451047/national-survey-of-japanese-patients-with-mevalonate-kinase-deficiency-reveals-distinctive-genetic-and-clinical-characteristics
#1
Takayuki Tanaka, Kohei Yoshioka, Ryuta Nishikomori, Hidemasa Sakai, Junya Abe, Yuriko Yamashita, Ryugo Hiramoto, Akira Morimoto, Eiichi Ishii, Hirokazu Arakawa, Utako Kaneko, Yusei Ohshima, Nami Okamoto, Osamu Ohara, Ikue Hata, Yosuke Shigematsu, Tomoki Kawai, Takahiro Yasumi, Toshio Heike
OBJECTIVES: Mevalonate kinase deficiency (MKD), a rare autosomal recessive autoinflammatory syndrome, is caused by disease-causing variants of the mevalonate kinase gene. A national survey was undertaken to investigate clinical and genetic features of MKD patients in Japan. METHODS: The survey identified ten patients with MKD. Clinical information and laboratory data were collected from medical records and by direct interviews with patients, their families, and their attending physicians...
February 16, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29445111/fluvastatin-protects-cochleae-from-damage-by-high-level-noise
#2
Claus-Peter Richter, Hunter Young, Sonja V Richter, Virginia Smith-Bronstein, Stuart R Stock, Xianghui Xiao, Carmen Soriano, Donna S Whitlon
Exposure to noise and ototoxic drugs are responsible for much of the debilitating hearing loss experienced by about 350 million people worldwide. Beyond hearing aids and cochlear implants, there have been no other FDA approved drug interventions established in the clinic that would either protect or reverse the effects of hearing loss. Using Auditory Brainstem Responses (ABR) in a guinea pig model, we demonstrate that fluvastatin, an inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, protects against loss of cochlear function initiated by high intensity noise...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29433218/application-of-high-throughput-pyrosequencing-in-the-analysis-of-microbiota-of-food-commodities-procured-from-small-and-large-retail-outlets-in-a-u-s-metropolitan-area-a-pilot-study
#3
Daleniece Higgins, Chandan Pal, Irshad M Sulaiman, Chunrong Jia, Tyler Zerwekh, Scot E Dowd, Pratik Banerjee
With the advent of high-throughput sequencing technologies, it is possible to comprehensively analyze the microbial community of foods without culturing them in the laboratory. The estimation of all microbes inhabiting a food commodity (food microbiota) therefore may shed light on the microbial quality and safety of foods. In this study, we utilized high-throughput pyrosequencing of 16S rRNA genes as well as traditional microbiological methods to evaluate the bacterial diversity and the predicted metabolic pathways associated with the bacterial communities of selected foods (romaine lettuce, cabbage, deli meat, and chicken legs, total 200 samples) procured from small and large retail outlets located in Memphis-Shelby County, Tennessee, USA...
March 2018: Food Research International
https://www.readbyqxmd.com/read/29430349/%C3%AE-ecdysterone-accumulation-and-regulation-in-ajuga-multiflora-bunge-suspension-culture
#4
Yan-Chen Wang, Jia-Jia Zhao, De-Fu Chi
Ajuga multiflora Bunge cells contain β-ecdysterone (β-EC) that regulates the molting process of insect larvae. In this study, different conditions of culture have been studied to optimize the production of β-EC. A. multiflora Bunge growth fitted the curve of logistic equation with one growth cycle of 17 days. The electric conductivity of medium had a negative correlation with not only the weight of dry cell but also the β-EC accumulation, and thus, could be used for monitoring the peak of both cell growth and β-EC accumulation...
February 2018: 3 Biotech
https://www.readbyqxmd.com/read/29407907/silver-complex-of-salicylic-acid-and-its-hydrogel-cream-in-wound-healing-chemotherapy
#5
Maria-Eleni K Stathopoulou, Christina N Banti, Nikolaos Kourkoumelis, Antonios G Hatzidimitriou, Angelos G Kalampounias, Sotiris K Hadjikakou
The known metallotherapeutic [Ag(salH)]2 (AGSAL-1) of salicylic acid (salH2), was used for the development of new efficient silver based material for wounds healing. AGSAL-1 was characterized by spectroscopic techniques and X-ray crystallography. The wound healing epithelialization of AGSAL-1 was investigated by the means of scratch assay against immortalized human keratinocytes (HaCaT) cells. The anti-inflammatory activity of AGSAL-1 was evaluated by monitoring the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX)...
February 1, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29406718/metabolomics-analysis-reveals-that-ethylene-and-methyl-jasmonate-regulate-different-branch-pathways-to-promote-the-accumulation-of-terpenoid-indole-alkaloids-in-catharanthus-roseus
#6
Xiao-Ning Zhang, Jia Liu, Yang Liu, Yu Wang, Ann Abozeid, Zhi-Guo Yu, Zhong-Hua Tang
The medicinal plant Catharanthus roseus accumulates large numbers of terpenoid indole alkaloids (TIAs), including the pharmaceutically important vinblastine, vincristine, ajmalicine, and serpentine. The phytohormone ethylene or methyl jasmonate (MeJA) can markedly enhance alkaloid accumulation. The interaction between ethylene or MeJA in the regulation of TIA biosynthesis in C. roseus is unknown. Here, a metabolomics platform is reported that is based on liquid chromatography (LC) coupled with time-of-flight mass spectrometry to study candidate components for TIA biosynthesis, which is controlled by ethylene or MeJA in C...
February 6, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29402381/mitochondrial-coq-deficiency-is-a-common-driver-of-mitochondrial-oxidants-and-insulin-resistance
#7
Daniel J Fazakerley, Rima Chaudhuri, Pengyi Yang, Ghassan J Maghzal, Kristen C Thomas, James R Krycer, Sean J Humphrey, Benjamin L Parker, Kelsey H Fisher-Wellman, Christopher C Meoli, Nolan J Hoffman, Ciana Diskin, James G Burchfield, Mark J Cowley, Warren Kaplan, Zora Modrusan, Ganesh Kolumam, Jean Yh Yang, Daniel L Chen, Dorit Samocha-Bonet, Jerry R Greenfield, Kyle L Hoehn, Roland Stocker, David E James
Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity...
February 6, 2018: ELife
https://www.readbyqxmd.com/read/29394220/beneficial-effect-of-atorvastatin-modified-dendritic-cells-pulsed-with-myelin-oligodendrocyte-glycoprotein-autoantigen-on-experimental-autoimmune-encephalomyelitis
#8
Zhibo Chen, Dehao Yang, Xiao Peng, Jie Lin, Zhongqian Su, Jia Li, Xu Zhang, Yiyun Weng
It is well known that dendritic cells play a key role in producing antigen-specific responses. Inversely, tolerogenic dendritic cells (TolDCs), a specialized subset, induce immune tolerance and negatively regulate autoimmune responses. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the mevalonate pathway for cholesterol biosynthesis, might be a promising inductive agent for inducing TolDCs. This study aimed to investigate the effectiveness of TolDCs induced by atorvastatin pulsed with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55) in experimental autoimmune encephalomyelitis mice established by MOG35-55 immunization and to investigate the potential effects on Th17/Treg balance in the murine model of multiple sclerosis...
February 1, 2018: Neuroreport
https://www.readbyqxmd.com/read/29392731/immune-modulatory-effects-of-statins
#9
REVIEW
Robert Zeiser
Despite major advances in recent years, immunosuppressive regimens for multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and graft-versus-host disease (GVHD) have still major side effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate limiting enzyme of the L-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the L-mevalonate pathway reduces inflammation via effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane...
February 2, 2018: Immunology
https://www.readbyqxmd.com/read/29374778/respiratory-deficiency-in-yeast-mevalonate-kinase-deficient-may-explain-mkd-associate-metabolic-disorder-in-humans
#10
Manuella Maria Silva Santos, Carolina Elsztein, Rafael Barros De Souza, Sérgio de Sá Leitão Paiva, Jaqueline Azevêdo Silva, Sergio Crovella, Marcos Antonio De Morais
Mevalonate kinase deficiency (MKD) an orphan drug rare disease affecting humans with different clinical presentations, is still lacking information about its pathogenesis; no animal or cell model mimicking the genetic defect, mutations at MVK gene, and its consequences on the mevalonate pathway is available. Trying to clarify the effects of MVK gene impairment on the mevalonate pathway we used a yeast model, the erg12-d mutant strain Saccharomyces cerevisiae (orthologous of MKV) retaining only 10% of mevalonate kinase (MK) activity, to describe the effects of reduced MK activity on the mevalonate pathway...
January 27, 2018: Current Genetics
https://www.readbyqxmd.com/read/29372902/crystal-structure-of-cytoplasmic-acetoacetyl-coa-thiolase-from-saccharomyces-cerevisiae
#11
Pengfei Zhou, Zhongliang Zhu, Muhammad Hidayatullah Khan, Peiyi Zheng, Maikun Teng, Liwen Niu
Thiolases are vital enzymes which participate in both degradative and biosynthetic pathways. Biosynthetic thiolases catalyze carbon-carbon bond formation by a Claisen condensation reaction. The cytoplasmic acetoacetyl-CoA thiolase from Saccharomyces cerevisiae, ERG10, catalyses carbon-carbon bond formation in the mevalonate pathway. The structure of a S. cerevisiae biosynthetic thiolase has not previously been reported. Here, crystal structures of apo ERG10 and its Cys91Ala variant were solved at resolutions of 2...
January 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/29372683/the-role-of-statins-as-therapeutic-agents-in-cancer
#12
REVIEW
Jana Sopková, Eva Vidomanová, Ján Strnádel, Henrieta Škovierová, Erika Halašová
Statins are the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This enzyme catalyzes conversion of HMG-CoA to mevalonate, which are the intermediates in cholesterol biosynthetic pathway. Statins also play an important role in carcinogenesis, because they are able to affect the cancer cell metabolism. Their effect has been observed in several cellular processes, such as angiogenesis, metastasis, apoptosis and cell proliferation. However, these effects are highly dependent on type of cancer and individual statins vary in their antitumor potential...
December 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29355536/a-mathematical-model-of-the-mevalonate-cholesterol-biosynthesis-pathway
#13
Frances Pool, Richard Currie, Peter K Sweby, José Domingo Salazar, Marcus J Tindall
We formulate, parameterise and analyse a mathematical model of the mevalonate pathway, a key pathway in the synthesis of cholesterol. Of high clinical importance, the pathway incorporates rate limiting enzymatic reactions with multiple negative feedbacks. In this work we investigate the pathway dynamics and demonstrate that rate limiting steps and negative feedbacks within it act in concert to tightly regulate intracellular cholesterol levels. Formulated using the theory of nonlinear ordinary differential equations and parameterised in the context of a hepatocyte, the governing equations are analysed numerically and analytically...
January 17, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29349039/engineering-escherichia-coli-for-the-production-of-terpene-mixture-enriched-in-caryophyllene-and-caryophyllene-alcohol-as-potential-aviation-fuel-compounds
#14
Weihua Wu, Fang Liu, Ryan W Davis
Recent studies have revealed that caryophyllene and its stereoisomers not only exhibit multiple biological activities but also have desired properties as renewable candidates for ground transportation and jet fuel applications. This study presents the first significant production of caryophyllene and caryolan-1-ol by an engineered E. coli with heterologous expression of mevalonate pathway genes with a caryophyllene synthase and a caryolan-1-ol synthase. By optimizing metabolic flux and fermentation parameters, the engineered strains yielded 449 mg/L of total terpene, including 406 mg/L sesquiterpene with 100 mg/L caryophyllene and 10 mg/L caryolan-1-ol...
June 2018: Metabolic Engineering Communications
https://www.readbyqxmd.com/read/29338971/atorvastatin-impaired-glucose-metabolism-in-c2c12-cells-partly-via-inhibiting-cholesterol-dependent-glucose-transporter-4-translocation
#15
Binbin Sun, Zeyu Zhong, Fan Wang, Jiong Xu, Feng Xu, Weimin Kong, Zhaoli Ling, Nan Shu, Ying Li, Tong Wu, Mian Zhang, Liang Zhu, Xiaodong Liu, Li Liu
Skeletal muscle accounts for approximately 75% of glucose disposal in body and statins impair glucose metabolism. We aimed to investigate the effect of atorvastatin on glucose metabolism in C2C12 cells. Glucose metabolism and expression of glucose transporter 4 (GLUT4) and hexokinase II (HXKII) were measured following incubation with atorvastatin or pravastatin. Roles of cholesterol in atorvastatin-induced glucose metabolism impairment were investigated via adding cholesterol or mevalonic acid and confirmed by cholesterol depletion with methyl-β-cyclodextrin...
January 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29337059/fpps-mediates-tgf-%C3%AE-1-induced-non-small-cell-lung-cancer-cell-invasion-and-the-emt-process-via-the-rhoa-rock1-pathway
#16
Lin Lin, Ming Li, Lei Lin, Xiaolin Xu, Gening Jiang, Liang Wu
Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, was recently shown to play a role in cancer progression. However, its role in non-small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain unclear. In this study, FPPS expression was significantly correlated with TNM stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-β1-induced cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS expression of FPPS was induced by TGF-β1 and FPPS promoted cell invasion and EMT via the RhoA/Rock1 pathway...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29335349/efficacy-of-continuous-interleukin-1-blockade-in-mevalonate-kinase-deficiency-a-multicenter-retrospective-study-in-13-adult-patients-and-literature-review
#17
Samuel Deshayes, Sophie Georgin-Lavialle, Arnaud Hot, Cécile-Audrey Durel, Eric Hachulla, Nicolas Rouanes, Sylvain Audia, Thomas Le Gallou, Pierre Quartier, Geoffrey Urbanski, Laurent Messer, Stéphane Klein, Hubert de Boysson, Boris Bienvenu, Gilles Grateau, Achille Aouba
OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively...
January 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29328908/metabolic-induction-of-trained-immunity-through-the-mevalonate-pathway
#18
Siroon Bekkering, Rob J W Arts, Boris Novakovic, Ioannis Kourtzelis, Charlotte D C C van der Heijden, Yang Li, Calin D Popa, Rob Ter Horst, Julia van Tuijl, Romana T Netea-Maier, Frank L van de Veerdonk, Triantafyllos Chavakis, Leo A B Joosten, Jos W M van der Meer, Henk Stunnenberg, Niels P Riksen, Mihai G Netea
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29320955/therapeutic-roles-of-statins-in-gynecology-and-obstetrics-the-current-evidence
#19
Burak Zeybek, Maged Costantine, Gokhan S Kilic, Mostafa A Borahay
INTRODUCTION: Statins are a class of drugs, which act by inhibiting the rate-limiting enzyme of cholesterol biosynthesis (3-hydroxy-3-methyl-glutaryl-CoA reductase). The inhibition of mevalonate synthesis leads to subsequent inhibition of downstream products of this pathway, which explains the pleiotropic effects of these agents in addition to their well-known lipid-lowering effects. Accumulating evidence suggests that statins might be beneficial in various obstetric and gynecologic conditions...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29319354/inhibition-of-the-rhoa-rho-associated-coiled-coil-containing-protein-kinase-1-pathway-is-involved-in-the-therapeutic-effects-of-simvastatin-on-pulmonary-arterial-hypertension
#20
Wei-Hua Liu, Xiao-Hong Xu, Qin Luo, Hong-Liang Zhang, Yong Wang, Qun-Ying Xi, Zhi-Hui Zhao, Zhi-Hong Liu
BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i...
January 10, 2018: Clinical and Experimental Hypertension: CHE
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