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31.
The importance of morphogenetic proteins (BMPs) and their antagonists in vascular development is increasingly being recognized. BMP-4 is essential for angiogenesis and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both induced by the activin receptor like-kinase 1 (ALK1) when stimulated by BMP-9. In this study, however, we show that CV2 preferentially binds and inhibits BMP-9 thereby providing strong feedback inhibition for BMP-9/ALK1 signaling rather than for BMP-4/ALK2 signaling. CV2 disrupts complex formation involving ALK2, ALK1, BMP-4, and BMP-9 required for the induction of both BMP antagonists. It also limits VEGF expression, proliferation, and tube formation in ALK1-expressing endothelial cells. In vivo, CV2 deficiency translates into a dysregulation of vascular BMP signaling, resulting in an abnormal endothelium with increased endothelial cellularity and expression of lineage markers for mature endothelial cells. Thus, mutual regulation by BMP-9 and CV2 is essential in regulating the development of the vascular endothelium. 相似文献
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Adrián Llerena Raul Allan Kiivet Marja-Liisa Dahl Javier Sánchez Vega Ly Rootslane Björn Wettermark 《Nordic journal of psychiatry》2013,67(1):61-65
The use of psychotropic drugs in the university hospitals in Tartu, Estonia; Huddinge, Sweden; and Badajoz, Spain, were studied, using the defined daily doses per 100 bed-days (DDD/100 bed-days) method. The total amount of drugs used in the surgical and medical departments was 50 DDD/100 bed-days in Huddinge, versus 33 and 14 DDD/100 bed-days in Tartu and Badajoz, respectively. Barbiturates accounted for 35% of all psychotropics in Tartu but were practically not used in Huddinge. In contrast, antidepressants were practically not used in Tartu. The use of psychotropic drugs in the intensive care units was highest in Huddinge (320 DDD/100 bed-days), compared with Tartu and Badajoz (177 and 96 DDD/100 bed-days, respectively). The frequency of psychotropic drug use were strikingly different in the three hospitals studied. 相似文献
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Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice 总被引:1,自引:0,他引:1
Susanne?M.?HenningEmail authorView authors OrcID profile Jieping?Yang Mark?Hsu Ru-Po?Lee Emma?M.?Grojean Austin?Ly Chi-Hong?Tseng David?Heber Zhaoping?Li 《European journal of nutrition》2018,57(8):2759-2769
Purpose
Decaffeinated green tea (GT) and black tea (BT) polyphenols inhibit weight gain in mice fed an obesogenic diet. Since the intestinal microflora is an important contributor to obesity, it was the objective of this study to determine whether the intestinal microflora plays a role in the anti-obesogenic effect of GT and BT.Methods
C57BL/6J mice were fed a high-fat/high-sucrose diet (HF/HS, 32% energy from fat; 25% energy from sucrose) or the same diet supplemented with 0.25% GTP or BTP or a low-fat/high-sucrose (LF/HS, 10.6% energy from fat, 25% energy from sucrose) diet for 4 weeks. Bacterial composition was assessed by MiSeq sequencing of the 16S rRNA gene.Results
GTP and BTP diets resulted in a decrease of cecum Firmicutes and increase in Bacteroidetes. The relative proportions of Blautia, Bryantella, Collinsella, Lactobacillus, Marvinbryantia, Turicibacter, Barnesiella, and Parabacteroides were significantly correlated with weight loss induced by tea extracts. BTP increased the relative proportion of Pseudobutyrivibrio and intestinal formation of short-chain fatty acids (SCFA) analyzed by gas chromatography. Cecum propionic acid content was significantly correlated with the relative proportion of Pseudobutyrivibrio. GTP and BTP induced a significant increase in hepatic 5′adenosylmonophosphate-activated protein kinase (AMPK) phosphorylation by 70 and 289%, respectively (P < 0.05) determined by Western blot.Conclusion
In summary, both BTP and GTP induced weight loss in association with alteration of the microbiota and increased hepatic AMPK phosphorylation. We hypothesize that BTP increased pAMPK through increased intestinal SCFA production, while GTPs increased hepatic AMPK through GTP present in the liver.35.
O’Neill Joseph O’Connor Mary J. Kalender Guldamla Ly Ronald Ng Andrea Dillon Andrea Narr Katherine L. Loo Sandra K. Alger Jeffry R. Levitt Jennifer G. 《Brain imaging and behavior》2022,16(1):69-77
Brain Imaging and Behavior - In many patients, ostensible idiopathic attention deficit-hyperactivity disorder (ADHD) may actually stem from covert prenatal alcohol exposure (PAE), a... 相似文献
36.
Herbal remedies have been considered as potential medication for diabetes type 2 treatment. Bitter melons, onions, or Goryeong Ginsengs are popular herbals and their functions in diabetes patients have been well documented. Recently, the Euphorbia hirta has been shown to have strong effects on diabetes in mice, however, there has been no research clearly indicating what the active compound is. The main purpose of the current study was therefore to evaluate whether a relationship exists between various bioactive compounds in E. hirta Linn and targeted protein relating diabetes type 2 in human. In view of this, extraction from E. hirta Linn was tested if they contained the bioactive compounds. This process involved the docking of 3D structures of those substances (ligand) into targeted proteins: 11-β hydroxysteroid dehydrogenase type 1, glutamine: fructose-6-phosphate amidotransferase, protein phosphatase, and mono-ADP-ribosyltransferase sirtuin-6. Then, LigandScout was applied to evaluate the bond formed between ligand and the binding pocket in the protein. These test identified in eight substances with high binding affinity (<?8.0 kcal/mol) to all four interested proteins of this article. The substances are quercetrin, rutin, myricitrin, cyanidin 3,5-O-diglucoside, pelargonium 3,5-diglucose in “flavonoid family” and α-amyrine, β-amyrine, taraxerol in “terpenes group.” The result can be explained by the 2D picture which showed hydrophobic interaction, hydrogen bond acceptor, and hydrogen bond donor forming between carbonyl oxygen molecules of ligand with free residues in the protein. These pictures of the bonding provide evidence that E. hirta Linn may prove to be an effective treatment for diabetes type 2. 相似文献
37.
All-trans retinoic acid (RA) is a potent inducer of regeneration. Because the liver is the principal site for storage and bioactivation of vitamin A, the current study examines the effect of RA in mouse hepatocyte proliferation and liver regeneration. Mice that received a single dose of RA (25 μg/g) by oral gavage developed hepatomegaly with increased number of Ki67-positive cells and induced expression of cell cycle genes in the liver. DNA binding data revealed that RA receptors retinoic acid receptor β (RARβ) and retinoid x receptor α (RXRα) bound to cell cycle genes Cdk1, Cdk2, Cyclin B, Cyclin E, and Cdc25a in mice with and without RA treatment. In addition, RA treatment induced novel binding of RARβ/RXRα to Cdk1, Cdk2, Cyclin D, and Cdk6 genes. All RARβ/RXRα binding sites contained AGGTCA-like motifs. RA treatment also promoted liver regeneration after partial hepatectomy (PH). RA signaling was implicated in normal liver regeneration as the mRNA levels of RARβ, Aldh1a2, Crabp1, and Crbp1 were all induced 1.5 days after PH during the active phase of hepatocyte proliferation. RA treatment prior to PH resulted in early up-regulation of RARβ, Aldh1a2, Crabp1, and Crbp1, which was accompanied by an early induction of cell cycle genes. Western blotting for RARβ, c-myc, Cyclin D, E, and A further supported the early induction of retinoid signal and cell proliferation by RA treatment. Taken together, our data suggest that RA may regulate cell cycle progression and accelerates liver regeneration. Such effect is associated with an early induction of RA signaling, which includes increased expression of the receptor, binding proteins, and processing enzyme for retinoids. 相似文献
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