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Juan Luis Carrillo-Linares, María Inmaculada García-Fernández, María José Morillo, Purificación Sánchez, José Rioja, Francisco Javier Barón, María José Ariza, Dominic J Harrington, David Card, Federica Boraldi, Daniela Quaglino, Pedro Valdivielso
Introduction: Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene. Vitamin K1 is involved in the posttranslational carboxylation of some proteins related to inhibition of the calcification process. Our aim was to investigate, in patients affected by PXE, baseline levels of vitamin K1 -dependent proteins and -metabolites and whether parenteral administration of phytomenadione was effective in modulating their levels. Methods: We included eight PXE patients with typical clinical symptoms (skin, retina, and vascular calcification) and two ABCC6 causative mutations; 13 clinically unaffected first-degree patients' relatives (9 carrying one ABCC6 mutation and 4 non-carriers)...
2018: Frontiers in Medicine
Sissel Beate Rønning, Mona Elisabeth Pedersen, Ragnhild Stenberg Berg, Bente Kirkhus, Rune Rødbotten
Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells...
2018: PloS One
Eva Klapkova, Jana Cepova, Katerina Dunovska, Richard Prusa
BACKGROUND: New high-performance liquid chromatography (HPLC) method was developed for the determination of vitamin K1 and two forms of vitamin K2 (MK-4 and MK-7) in human serum, and the levels of vitamin K were determined in 350 samples of postmenopausal women. METHODS: Vitamin K was determined by HPLC with fluorescence detection after postcolumn zinc reduction. The detection was performed at 246 nm (excitation) and 430 nm (emission). The internal standard and 2 mL of ethanol were added to 500 μL of serum...
January 15, 2018: Journal of Clinical Laboratory Analysis
Yan Liu, Zi-Ming Yang, Zheng-Lian Xue, Zhou Wang, Shi-Guang Zhao, Long-Bao Zhu, Liu-Xiu Hu, Xiu-Min Ding, Yun Su
Menaquinone (MK) has important applications in the pharmaceutical and food industries. To increase the production rate (QP ) of MK-4, we developed a straightforward biotransformation method for MK-4 synthesis directly from its precursors 1,4-dihydroxy-2-naphthoate (DHNA) and farnesol using whole cells of genetically engineered Elizabethkingia meningoseptica. Results showed that MK-4 can be produced directly from farnesol and DHNA using both free and immobilized FM-D198 cells. MK-4 yield peaked at 29.85 ± 0...
November 27, 2017: World Journal of Microbiology & Biotechnology
Hongfei Wei, Genhai Zhao, Hui Liu, Han Wang, Wenfeng Ni, Peng Wang, Zhiming Zheng
Menaquinone homologs (MK-n), that is, MK-4, MK-5, and MK-6, can be produced by the fermentation of Flavobacterium. In this study, we proposed a simple and efficient method for the extraction of menaquinones from wet cells without the process of drying the biomass. Meanwhile, a rapid and effective solution for the separation of menaquinone homologs was developed using a single organic solvent, which was conducive to the recovery of the solvent. The results showed that the highest yield was obtained with pretreatment using absolute ethanol at a ratio of 6:1 (v/m) for 30 min and then two extractions of 30 min each using methanol at a ratio of 6:1 (v/m)...
January 2018: Bioprocess and Biosystems Engineering
Midori Katsuyama, Masashi Demura, Hironobu Katsuyama, Hideji Tanii, Kiyofumi Saijoh
The aim of the present study was to determine the molecular basis of the beneficial effects of genistein and/or menaquinone‑4 (MK‑4) on bone quality. Initially, 1 µM genistein was applied to MC3T3‑E1 cells for 24 h and the upregulated mRNAs that were detected by microarray were selected for further examination by reverse transcription‑quantitative‑polymerase chain reaction. Among them, alterations were observed in the level of GATA‑binding protein 6 (GATA6), Notch gene homolog 2 (NOTCH2), Wnt family member 5A (WNT5A), bone γ‑carboxyglutamate protein (BGLAP), chondroadherin (CHAD), dipeptidyl peptidase 4 (DPP4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), alkaline phosphatase (ALP) 3 and ATPase phospholipid‑transporting 11A (ATP11A) in response to treatment with 0...
July 2017: Molecular Medicine Reports
Domitilla Mandatori, Letizia Penolazzi, Caterina Pipino, Pamela Di Tomo, Sara Di Silvestre, Natalia Di Pietro, Sara Trevisani, Marco Angelozzi, Mariangela Ucci, Roberta Piva, Assunta Pandolfi
Menaquinones, also known as Vitamin K2 family, regulate calcium homeostasis in a 'bone-vascular cross-talk' and recently received particular attention for their positive effect on bone formation. Given that the correlation between menaquinones and bone metabolism to date is still unclear, the objective of our study was to investigate the possible role of menaquinone-4 (MK-4), an isoform of the menaquinones family, in the modulation of osteogenesis. For this reason, we used a model of human amniotic fluid mesenchymal stem cells (hAFMSCs) cultured both in two-dimensional (2D) and three-dimensional (3D; RCCS™bioreactor) in vitro culture systems...
February 2018: Journal of Tissue Engineering and Regenerative Medicine
Naeti Suksomboon, Nalinee Poolsup, Htoo Darli Ko Ko
OBJECTIVE: To perform a systematic review and meta-analysis of randomized, placebo-controlled trials to assess the effect of vitamin K supplementation on insulin sensitivity. DATA SOURCES: MEDLINE, the Cochrane Library, CINAHL, Web of Science, Scopus,, and were searched up to January 2017. Reference lists of related papers were also scanned. STUDY SELECTION: Randomized controlled trials were selected if they compared vitamin K supplementation with placebo or no treatment and reported homeostasis model assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein, adiponectin, leptin, or interleukin-6 levels...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy
Menaquinone (MK) biosynthesis pathway is a potential target for evaluating antimicrobials in gram-positive bacteria. Here, 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) was targeted to reduce methicillin-resistant Staphylococcus aureus (MRSA) growth. MenA inhibiting, long chain-based compounds were designed, synthesized and evaluated against MRSA and menaquinone utilizing bacteria in aerobic conditions. The results showed that these bacteria were susceptible to most of the compounds. Menaquinone (MK-4) supplementation rescued MRSA growth, suggesting these compounds inhibit MK biosynthesis...
January 10, 2017: Scientific Reports
Cees Vermeer, Cynthia van 't Hoofd, Marjo H J Knapen, Sofia Xanthoulea
Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro bioactivity resulting in 2.5 and 2-fold higher carboxylated osteocalcin synthesis in MG63 cells than menaquinone-4 (MK-4, form of vitamin K2). Longer side chain lengths resulted in lower bioactivity...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
Seiko Noda, Asako Yamada, Rieko Tanabe, Kanae Nakaoka, Takayuki Hosoi, Masae Goseki-Sone
Alkaline phosphatase (ALP) hydrolyzes several monophosphate esters into inorganic acid and alcohol. In humans, 4 kinds of ALP isozymes have been identified: tissue-nonspecific ALP, intestinal ALP, placental ALP, and germ cell ALP. Intestinal ALP is expressed at a high concentration in the brush border membrane of intestinal epithelial cells and is known to be affected by several kinds of nutrients, such as lipids, but the physiological function of intestinal ALP has remained elusive. Vitamin K is an essential cofactor for the posttranslational carboxylation of glutamate residues into γ-carboxy glutamate...
November 2016: Nutrition Research
Kristin M McCabe, Sarah L Booth, Xueyan Fu, Emilie Ward, Michael A Adams, Rachel M Holden
BACKGROUND: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues. METHODS: In the present study, we assessed tissue concentrations of K1 and MK-4 and the expression of vitamin K-related genes in a rat model of adenine-induced CKD...
2017: American Journal of Nephrology
Hani M Khojah, Sameh Ahmed, Mahran S Abdel-Rahman, Khaled M Alkhalil, Al-Badr Hamza
The aim of this study was to evaluate the possible role of vitamin K homologs as potential biomarkers for disease activity in patients with rheumatoid arthritis (RA). In this study, 42 patients with RA and 40 healthy controls were enrolled. Serum levels of vitamin K homologs were measured using a high-performance liquid chromatography-fluorescence method. Different biochemical and clinical markers for disease activity were measured and correlated with serum levels of vitamin K homologs. There were no significant differences between RA patients and healthy subjects in demographic data...
October 8, 2016: Journal of Bone and Mineral Metabolism
David K Cundiff, Paul S Agutter
BACKGROUND: Nutrition researchers recently recognized that deficiency of vitamin K2 (menaquinone: MK-4-MK-13) is widespread and contributes to cardiovascular disease (CVD). The deficiency of vitamin K2 or vitamin K inhibition with warfarin leads to calcium deposition in the arterial blood vessels. METHODS: Using publicly available sources, we collected food commodity availability data and derived nutrient profiles including vitamin K2 for people from 168 countries...
August 24, 2016: Curēus
Yan-Xia Yu, Yi-Pei Li, Feng Gao, Qing-Song Hu, Yan Zhang, Dong Chen, Guang-Hui Wang
AIM: Increasing evidence has shown that environmental factors such as rotenone and paraquat induce neuroinflammation, which contributes to the pathogenesis of Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying the repression by menaquinone-4 (MK-4), a subtype of vitamin K2, of rotenone-induced microglial activation in vitro. METHODS: A microglial cell line (BV2) was exposed to rotenone (1 μmol/L) with or without MK-4 treatment...
September 2016: Acta Pharmacologica Sinica
Toshio Okano
Vitamin K is a cofactor for γ-glutamyl carboxylase, which catalyzes the posttranslational conversion of specific glutamyl residues to γ-carboxyglutamyl residues in a variety of vitamin K-dependent proteins (VKDPs) involved in blood coagulation, bone and cartilage metabolism, signal transduction, and cell proliferation. Despite the great advances in the genetic, structural, and functional studies of VKDPs as well as the enzymes identified as part of the vitamin K cycle which enable it to be repeatedly recycled within the cells, little is known of the identity and roles of key regulators of vitamin K metabolism in mammals and humans...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Stephanie G Harshman, Xueyan Fu, J Philip Karl, Kathryn Barger, Stefania Lamon-Fava, Athan Kuliopulos, Andrew S Greenberg, Donald Smith, Xiaohua Shen, Sarah L Booth
BACKGROUND: There has been limited characterization of biological variables that impact vitamin K metabolism. This gap in knowledge can limit the translation of data obtained from preclinical animal studies to future human studies. OBJECTIVE: The purpose of this study was to determine the effects of diet, sex, and housing on serum, tissue, and fecal vitamin K concentrations and gene expression in C57BL6 mice during dietary vitamin K manipulation. METHODS: C57BL6 4-mo-old male and female mice were randomly assigned to conventional or suspended-wire cages and fed control [1400 ± 80 μg phylloquinone (PK)/kg] or deficient (31 ± 0...
August 2016: Journal of Nutrition
Yuji Ikari, Sho Torii, Atsushi Shioi, Toshio Okano
BACKGROUND: Dietary intake of vitamin K has been reported to reduce coronary artery calcification (CAC) and cardiovascular events. However, it is unknown whether supplemental menaquinone (MK)-4 can reduce CAC or arterial stiffness. To study the effect of MK-4 supplementation on CAC and brachial ankle pulse wave velocity (baPWV). METHODS: This study is a single arm design to take 45 mg/day MK-4 daily as a therapeutic drug for 1 year. Primary endpoint was CAC score determined using 64-slice multislice CT (Siemens), and the secondary endpoint was baPWV measured before and 1 year after MK-4 therapy...
May 12, 2016: Nutrition Journal
Guylaine Ferland, Isabelle Doucet, Dominique Mainville
Whether through the vitamin K-dependent proteins or the individual K vitamers, vitamin K (VK) is associated with a number of age-related conditions (e.g., osteoporosis, atherosclerosis, insulin resistance, cognitive decline). In light of this, we investigated the influence of lifetime dietary VK exposure on the tissue distribution of phylloquinone (K₁) and menaquinone-4 (MK-4) vitamers in 3-, 12- and 22-month-old male and female rats fed different K₁ diets since weaning or subjected to a 40% calorie restricted diet (CR) since adulthood...
March 4, 2016: Nutrients
Ineke J Riphagen, Jan C van der Molen, Martijn van Faassen, Gerjan Navis, Martin H de Borst, Frits A J Muskiet, Wilhelmina H A de Jong, Stephan J L Bakker, Ido P Kema
BACKGROUND: Given the growing interest in the health benefits of vitamin K, there is great need for development of new high-throughput methods for quantitative determination of vitamin K in plasma. We describe a simple and rapid method for measurement of plasma vitamin K1 (phylloquinone [PK]) and K2 (menaquinones [MK]-4 and -7). Furthermore, we investigated the association of fasting plasma vitamin K with functional vitamin K insufficiency in renal transplant recipients (RTR). METHODS: We used HPLC-tandem mass spectrometry with atmospheric pressure chemical ionization for measurement of plasma PK, MK-4, and MK-7...
July 1, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
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