torsdag 20 oktober 2016

K-vitamiini ja nivelreuma

 Nivelreuma potilailla tämän tutkimuksen mukaan merkitsijät K-vitamiinista ja  K-vitamiinivajeesta osoittivat seuraavaa:
K-vitamiini vajetta merkitsevä  ucOC ( alikarboksyloitunut osteokalsiini)  oli koholla, myös  matrixmetalloproteinaasi 3 koholla.
Sen sijaan varsinainen  K-vitamiini itse,  menakinonilajit  MK-4, MK-7 ja  fyllokinoni (PK) olivat seerumipitoisuuksiltaan alentuneet,.
joten näiden kahden indikaattoriryhmän korrelaatio keskenään oli käänteinen.
Vitamiini K:n homologeja   voitaneen käyttää nivelreuman aktiivisuuden merkitsijöinä.

LÄHDE: https://www.ncbi.nlm.nih.gov/pubmed/27722902

J Bone Miner Metab. 2016 Oct 8. [Epub ahead of print]

Vitamin K homologs as potential biomarkers for disease activity in patients with rheumatoid arthritis.

Abstract

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. Patients with RA showed significantly higher levels of biochemical markers compared with healthy subjects (p < 0.001). These markers included rheumatoid factor (RF), anticyclic citrullinated polypeptide (anti-CCP), undercarboxylated osteocalcin (ucOC), matrix metalloproteinase (MMP-3), C-reactive protein (CRP), and disease activity score assessing 28 joints with erythrocyte sedimentation rate (DAS28-ESR). In addition, serum levels of vitamin K homologs were reduced in RA patients, and the levels of menaquinone-4 (MK-4) and menaquinone-7 (MK-7) were moderately to strongly inversely correlated with the clinical articular features in RA patients, whereas phylloquinone (PK) levels were weakly correlated. Serum levels of MK-4, MK-7 and PK were strongly inversely correlated with ucOC, MMP-3 and DAS28-ESR in RA patients. In contrast, serum levels of MK-4, MK-7 and PK were weakly correlated with CRP, RF and anti-CCP. These results suggest that serum levels of vitamin K homologs may be considered as potential biomarkers for disease activity. In addition, the results confirm the role of vitamin K deficiency in the etiology of RA.
KEYWORDS:
Biomarkers; DAS28-ESR; Matrix metalloproteinase; Rheumatoid arthritis; Vitamin K homologs
PMID:
27722902
DOI:
10.1007/s00774-016-0785-4
[PubMed - as supplied by publisher]

Menakinonin biosynteesin entsyymistä UBIAD1

 Geranyl-geranyylisääteinen prenyylitransferaasiUBIAD1:n -kuljetus ER ja Golgin kalvostojen välillä.
LÄHDE: https://www.ncbi.nlm.nih.gov/pubmed/27121042
J Lipid Res. 2016 Jul;57(7):1286-99. doi: 10.1194/jlr.M068759. Epub 2016 Apr 27.

Geranylgeranyl-regulated transport of the prenyltransferase UBIAD1 between membranes of the ER and Golgi. Schumacher MM1, Jun DJ1, Jo Y1, Seemann J2, DeBose-Boyd RA3.Erratum in  [J Lipid Res. 2016]

Tiivistelmästä, Abstract

 UBIAD1 hyödyntää geranylgeranyylipyrofosfaattia (GGpp) syntetisoidessaan  K2 vitamiinia menakinonialalajia MK-4.
Aiemmin tutkijat olivat havainneet, että sterolit liipaisevat esiin UBIAD1:n kiinnittymisen  HMG-CoA-reduktaasiin, joka lokalisoituu endoplasmiseen verkostoon (ER). Mainittu HMG-CoA on taas kolesterolisynteesin ja nonsteroidi-isopreenien  (kuten GGpp)  syntesin  tahtia  rajoittava (säätelevä)  entsyymi.
UBIAD1-sitoutuminen HMG-CoAreduktaasiin estää  sterolien kiihdyttämän reduktaasin hajottamisen, jonka tehtävä olisi  antaa   feed back säätöä entsyymille.
Jos soluun lisätään GGOH ( geranylgeraniolia, joka voi muuttua GGpp muotoon), triggeröityy UBIAD1:n vapautuminen rfeduktaasista, jolloin reduktaasi voi maksimaalsiesti hajota ja silloin salliutuu UBIAD1:n kulkeutuminen ER:stä Golgiin. Tutkijat luonnehtivat edellen tätä geranylgeraniolisääteistä UBIAD1- kuljetusta.

  • UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4. Previously, we found that sterols trigger binding of UBIAD1 to endoplasmic reticulum (ER)-localized HMG-CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids, including GGpp. This binding inhibits sterol-accelerated degradation of reductase, which contributes to feedback regulation of the enzyme. The addition to cells of geranylgeraniol (GGOH), which can become converted to GGpp, triggers release of UBIAD1 from reductase, allowing for its maximal degradation and permitting ER-to-Golgi transport of UBIAD1. Here, we further characterize geranylgeranyl-regulated transport of UBIAD1. 

Tulokset tästä luonnehtimisesta puoltavat  sellaista mallia, missä UBIAD1 suorittaa jatkuvaa kiertämistä   endoplasmisen retikulumin (ER)  ja  keski- ja trans-Golgin laitteen  välillä  soluissa, joissa on isoprenoideja.  Jos GGpp vähenee endoplasmisen retikulumin kalvostossa, UBIAD1 joutuu  loukkuun organellin sisään, missä se estää  reduktaasin  hajoamista.

  • Results of this characterization support a model in which UBIAD1 continuously cycles between the ER and medial-trans Golgi of isoprenoid-replete cells. Upon sensing a decline of GGpp in ER membranes, UBIAD1 becomes trapped in the organelle where it inhibits reductase degradation. 

 Eräässä silmän sarveiskalvon taudissa ( SCD) on havaittu liittymää  UBIAD1:n mutaatioon ja silloin  kertyy sarveiskalossa kolesterolia, joka saostuu endoplasmiseen retikulumiin ja blokeeraa reduktaasin hajoamisen.
  • Mutant forms of UBIAD1 associated with Schnyder corneal dystrophy (SCD), a human eye disease characterized by corneal accumulation of cholesterol, are sequestered in the ER and block reductase degradation. 

 Yhteenvetona nämä löydöt paljastavat uuden herkän  mekanismin, jolla   UBIAD1:n  solunsisäinen kulkeutuminen  kontrolloituu  tiukan  metabolisesti  ja  voi  suoraan moduloida reduktaasin hajomista  ja mikä  mekanismi  on  epäkunnnossa SCD-taudissa ( UBIAD1 entsyymin  mutaatiossa).

  • Collectively, these findings disclose  a novel sensing mechanism 
  • that allows for stringent metabolic control of intracellular trafficking of UBIAD1,
  •  which directly modulates reductase degradation
  •  and becomes disrupted in SCD. 

KEYWORDS:

UbiA prenyltransferase domain-containing protein-1; endoplasmic reticulum; isoprenoid; lipid metabolism; protein trafficking; vitamin K
PMID:
27121042
PMCID:
PMC4918857
[Available on 2017-07-01]
DOI:
10.1194/jlr.M068759

onsdag 22 april 2015

Lykopeeni (Karotinoidi) C40H56)

http://cebp.aacrjournals.org/content/5/10/823
 http://www.newyorkurologic.com/pdf/Lycopene.pdf

Alfa-karoteenilähteet ravinnossa

http://nutritiondata.self.com/foods-000134000000000000000.html
 http://www.endmemo.com/health/nutri2/acarotene.php
Listasta otettu esimerkkinä  vain 20 runsainta alfa-karoteenin lähdettä: 
No.
Food Name
ug
(in 100g food)
1 Pumpkin, canned, without salt 4795.102
2 Carrot juice, canned 4341.949
3 Carrots, cooked, boiled, drained, without salt 3776.282
4 Carrots, frozen, cooked, boiled, drained, without salt 3775.342
5 Carrots, baby, raw 3770
6 Carrots, raw 3477.272
7 Carrots, canned, regular pack, drained solids 2743.15
8 Vegetables, mixed, canned, drained solids 2636.196
9 Spices, chili powder 2076.923
10 Spices, parsley, dried 1461.538
11 Vegetables, mixed, frozen, cooked, boiled, drained, without salt 968.131
12 Pie, pumpkin, commercially prepared 686.238
13 Squash, winter, all varieties, cooked, baked, without salt 681.951
14 Soup, vegetable, canned, chunky, ready-to-serve, commercial 512.083
15 Plantains, raw 437.988
16 Beef stew, canned entree 356.034
17 Plantains, cooked 353.246
18 Pumpkin, cooked, boiled, drained, without salt 348.163
19 Pimento, canned 241.666
20 Vegetable juice cocktail, canned 209.917
















































































































































































































































Alfa-karoteenilla on antimetastaattista ominaisuutta (2015 tietoa)

J Nutr Biochem. 2015 Feb 14. pii: S0955-2863(15)00028-5. doi: 10.1016/j.jnutbio.2014.12.012. [Epub ahead of print]

Alpha-carotene inhibits metastasis in Lewis lung carcinoma in vitro, and suppresses lung metastasis and tumor growth in combination with taxol in tumor xenografted C57BL/6 mice.

Abstract

This study aimed to investigate the anti-metastatic activity of α-carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice. Cell culture studies reveal that AC significantly inhibited invasion, migration and activities of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator but increased protein expression of tissue inhibitor of MMP (TIMP)-1, -2 and plasminogen activator inhibitor (PAI)-1. 
 These effects of AC are similar to those of β-carotene at the same concentration (2.5μM). AC (2.5μM) also significantly inhibited integrin β1-mediated phosphorylation of focal adhesion kinase (FAK) which then decreased the phosphorylation of MAPK family. Findings from the animal model reveal that AC treatment (5mg/kg) alone significantly decreased lung metastasis without affecting primary tumor growth, whereas taxol treatment (6mg/kg) alone exhibited significant inhibition on both actions, as compared to tumor control group.
AC treatment alone significantly decreased protein expression of integrin β1 but increased protein expression of TIMP-1 and PAI-1 without affecting protein expression of TIMP-2 and phosphorylation of FAK in lung tissues, whereas taxol treatment alone significantly increased protein expression of TIMP-1, PAI-1 and TIMP-2 but decreased protein expression of integrin β1 and phosphorylation of FAK.
 The combined treatment produced stronger actions on lung metastasis and lung tissues protein expression of TIMP-1, TIMP-2 and PAI-1. Overall, we demonstrate that AC effectively inhibits LLC metastasis and suppresses lung metastasis in combination with taxol in LLC-bearing mice, suggesting that AC could be used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs.
Copyright © 2015. Published by Elsevier Inc.

KEYWORDS:

Lewis lung carcinoma; Metastasis; Taxol; α-Carotene; β-Carotene

Karotenoidien edullisuudesta (2015 tietoa)

Am J Clin Nutr. 2015 Apr 15. pii: ajcn105080. [Epub ahead of print]

Plasma carotenoids and risk of breast cancer over 20 y of follow-up.

Abstract

Increasing evidence suggests that carotenoids, which are micronutrients in fruit and vegetables, reduce breast cancer risk. Whether carotenoids are important early or late in carcinogenesis is unclear, and limited analyses have been conducted by breast tumor subtypes.
We sought to examine issues of the timing of carotenoid exposure as well as associations by breast tumor subtypes.
We conducted a nested case-control study of plasma carotenoids measured by using reverse-phase high-performance liquid chromatography and breast cancer risk in the Nurses' Health Study. In 1989-1990, 32,826 women donated blood samples; in 2000-2002, 18,743 of these women contributed a second blood sample. Between the first blood collection and June 2010, 2188 breast cancer cases were diagnosed (579 cases were diagnosed after the second collection) and matched with control subjects. RRs and 95% CIs were calculated by using conditional logistic regression adjusted for several breast cancer risk factors.
Higher concentrations of α-carotene, β-carotene, lycopene, and total carotenoids were associated with 18-28% statistically significant lower risks of breast cancer (e.g., β-carotene top compared with bottom quintile RR: 0.72; 95% CI: 0.59, 0.88; P-trend < 0.001). Associations were apparent for total carotenoids measured ≥10 y before diagnosis (top compared with bottom quintile RR: 0.69; 95% CI: 0.50, 0.95; P-trend = 0.01) as well as those...
CONCLUSION:
In this large prospective analysis with 20 y of follow-up, women with high plasma carotenoids were at reduced breast cancer risk particularly for more aggressive and ultimately fatal disease.
© 2015 American Society for Nutrition.
KEYWORDS:
biomarkers; breast cancer; carotenoids; nested case-control study; plasma

tisdag 21 april 2015

Onko luteiinista haittaa, milloin ja miksi?

http://www.livestrong.com/article/544317-the-disadvantages-of-lutein/
21.4. 2015
Tässä artikkelissa sanotaan luteiinista samaa kuin A-vitamiinista henkilöillä jotka polttavat ja joilla on keuhkosyövän riskiä.   Siis jatkokäytössä lisänä  ei niissä tapauksisa edullista ehkä. ainakaan  kohtuuttoman suuressa määrässää lisävalmisteena.