scholarly journals The amelioration of T2DM rat femoral bone achieved by anti-osteoporosis of caprine CSN1S2 protein through bone morphogenetic protein signaling pathway

2021 ◽  
Author(s):  
Fatchiyah Fatchiyah ◽  
Bambang Setiawan ◽  
Tomohiko Sasase ◽  
Takeshi Ohta
Keyword(s):  
Crystal Size ◽  
Protein Signaling ◽  
Femoral Bone ◽  
Granule Formation ◽  
Trabecular Thickness ◽  
Srage Level ◽  
Caprine Milk ◽  
Hydroxyapatite Crystal ◽  
Cellular Markers ◽  
High Level

We investigated the potential anti-glycation and anti-osteoporosis properties of Caprine milk CSN1S2 protein on the serum AGEs and sRAGE level, osteogenic factors expressions, femoral bone mesostructure, histomorphometry, and hydroxyapatite crystals changes in T2DM rats. Varying doses of Caprine milk CSN1S2 protein (0, 375, 750, and 1500mg/kg BW) were used to treat the control and T2DM rats. We measured AGEs and sRAGE level; RUNX2, OSX, BMP2, and Caspase-3 expressions in rats using ELISA and immunohistochemistry, respectively. The mesostructure and histomorphometry of femoral bone was analyzed using SEM Microscope and BoneJ software, then hydroxyapatite crystal size was determined using SEM-XRD. T2DM rats showed a high level of AGEs and a low level of sRAGE, the RUNX2, OSX, & BMP2 expression was down regulated, BV, BV.TV, Tb.Th, Tb.Sp, increased and SMI levels declined, respectively. Vice versa, after administration of the CSN1S2 protein to T2DM rats, improvement in all levels of molecular and cellular markers was achieved. In the CSN1S2 highest dose, AGEs level declined and sRAGE level elevated in T2DM rats. The 375 and 750 mg/kgBW of CSN1S2 protein was able to upregulate the RUNX2, OSX, and BMP2 expression in T2DM rats, thus improving the normalization of osteoclasts and osteoblasts number. The whole dose of CSN1S2 triggered the thickening of trabecular bone wall, granule formation, and normalized the trabecular thickness (Tb.Th) parameter of T2DM rats. The hydroxyapatite crystal size was increased in the highest dose of CSN1S2-treated T2DM rats. This study indicated that CSN1S2 protein had a protective effect against osteoporosis in the T2DM rat bones by means of glycation pathway inhibition, bone histomorphometry and mesostructure improvement via bone morphometric protein signaling.

The Effect of Temperature and Composition on Spinel Concentration and Crystal Size in High-Level Waste Glass

2001 ◽  
Author(s):  
Martin Mika ◽  
Milan Patek ◽  
Jaroslav Maixner ◽  
Simona Randakova ◽  
Pavel Hrma
Keyword(s):  
Crystal Size ◽  
Equilibrium Concentration ◽  
Effect Of Temperature ◽  
High Level Waste ◽  
Huge Number ◽  
Aluminoborosilicate Glass ◽  
High Level ◽  
The Cost ◽  
Different Content ◽  
The Mathematical Model

Abstract High-level radioactive wastes can be safely immobilized in alkali-aluminoborosilicate glass. To reduce the cost of the vitrification process, the waste loading should be maximized. This can be done by optimizing the process using mathematical modeling. The main objective of our work was to determine one of the necessary inputs for the mathematical model, which is the effect of temperature and composition on the concentration of spinel crystals and their size. We prepared six glasses with a different content of Li+, Na+, Mg2+, Ni2+, Cr3+, and SiIV and studied the effect of composition on the temperature dependence of spinel equilibrium concentration in glass by X-ray powder diffraction. The size of crystals was determined using optical microscopy. It was found that the temperature effect on spinel concentration significantly increased as the content of Ni2+ or Mg2+ in glass increased and slightly decreased as the content of Cr3+ increased and Li+ and Na+ content decreased. Both Ni2+ and Cr3+ acted as nucleating agents, producing a huge number of tiny spinel crystals (∼2 μm). In particular, Ni2+ seems to very significantly facilitate spinel crystallization.

scholarly journals The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal

2021 ◽  
Vol 17 (9) ◽  
pp. e1009364
Author(s):  
Hidetoshi Urakubo ◽  
Sho Yagishita ◽  
Haruo Kasai ◽  
Yoshiyuki Kubota ◽  
Shin Ishii
Keyword(s):  
Intracellular Signaling ◽  
Dopamine D2 Receptor ◽  
Experimental Studies ◽  
D2 Receptor ◽  
Long Term Potentiation ◽  
Projection Neurons ◽  
Protein Signaling ◽  
Dyt1 Dystonia ◽  
Term Potentiation ◽  
High Level

In behavioral learning, reward-related events are encoded into phasic dopamine (DA) signals in the brain. In particular, unexpected reward omission leads to a phasic decrease in DA (DA dip) in the striatum, which triggers long-term potentiation (LTP) in DA D2 receptor (D2R)-expressing spiny-projection neurons (D2 SPNs). While this LTP is required for reward discrimination, it is unclear how such a short DA-dip signal (0.5–2 s) is transferred through intracellular signaling to the coincidence detector, adenylate cyclase (AC). In the present study, we built a computational model of D2 signaling to determine conditions for the DA-dip detection. The DA dip can be detected only if the basal DA signal sufficiently inhibits AC, and the DA-dip signal sufficiently disinhibits AC. We found that those two requirements were simultaneously satisfied only if two key molecules, D2R and regulators of G protein signaling (RGS) were balanced within a certain range; this balance has indeed been observed in experimental studies. We also found that high level of RGS was required for the detection of a 0.5-s short DA dip, and the analytical solutions for these requirements confirmed their universality. The imbalance between D2R and RGS is associated with schizophrenia and DYT1 dystonia, both of which are accompanied by abnormal striatal LTP. Our simulations suggest that D2 SPNs in patients with schizophrenia and DYT1 dystonia cannot detect short DA dips. We finally discussed that such psychiatric and movement disorders can be understood in terms of the imbalance between D2R and RGS.

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

1996 ◽  
Vol 270 (1) ◽  
pp. E51-E59 ◽  
Author(s):  
D. A. Martinez ◽  
M. W. Orth ◽  
K. E. Carr ◽  
R. Vanderby ◽  
A. C. Vailas
Keyword(s):  
Growth Hormone ◽  
Bone Formation ◽  
Cortical Bone ◽  
Rapid Growth ◽  
Crystal Size ◽  
Bone Growth ◽  
Recombinant Human Growth Hormone ◽  
Bone Collagen ◽  
Bone Maturation ◽  
Hydroxyapatite Crystal

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

scholarly journals Identification of Inhibitors of HSF1 Functional Activity by High-Content Target-Based Screening

2009 ◽  
Vol 14 (10) ◽  
pp. 1165-1175 ◽  
Author(s):  
Qingyan Au ◽  
Yingjia Zhang ◽  
Jack R. Barber ◽  
Shi Chung Ng ◽  
Bin Zhang
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Small Molecule ◽  
Hela Cells ◽  
Significant Inhibition ◽  
Cancer Drug ◽  
Heat Shock Factor 1 ◽  
Mobility Shift ◽  
Granule Formation ◽  
High Level

Cancer cells are known to experience a high level of stress and may require constant repair for survival and proliferation. Recent studies showed that inhibition of heat shock factor 1 (HSF1), the key regulator for the stress-activated transcription of heat shock protein (HSP), can reduce the tumorigenic potential of cancer cells. Such a “nononcogene addiction” phenomenon makes HSF1 an attractive cancer drug target. Here, the authors report an image-based high-content screening (HCS) assay for HSF1 functional inhibitors. A heat shock—based methodology was used to stimulate the stress response followed by quantitative measurement of HSF1/HSP70 granules for compound-induced inhibitory effects. The authors discovered a small molecule from a compound library that inhibits HSF1 granule formation substantially in heat-shocked HeLa cells with IC50 at 80 nM. Electorphoretic mobility shift of HSF1 by this compound suggested significant inhibition of HSF1 phosphorylation, accompanied by reduced expression levels of HSP70 and HSP90 after heat induction. Importantly, HeLa cells stably transfected with HSF1 shRNA were more resistant to the compound treatment under lethal temperature than cells containing HSF1, further validating an HSF1-dependent mechanism of action. The HCS assay the authors developed was robust with a Z′ factor of 0.65 in a 384-well plate format, providing a valuable method for identifying small-molecule functional inhibitors of HSF1 for potential cancer treatment. ( Journal of Biomolecular Screening 2009:1165-1175)

scholarly journals Cross Talk between Insulin and Bone Morphogenetic Protein Signaling Systems in Brown Adipogenesis

2010 ◽  
Vol 30 (17) ◽  
pp. 4224-4233 ◽  
Author(s):  
Hongbin Zhang ◽  
Tim J. Schulz ◽  
Daniel O. Espinoza ◽  
Tian Lian Huang ◽  
Brice Emanuelli ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Cross Talk ◽  
Suppressive Effect ◽  
Bmp Signaling ◽  
Protein Signaling ◽  
Signaling Systems ◽  
Morphogenetic Protein ◽  
High Level ◽  
Signaling Components ◽  
Brown Adipogenesis

ABSTRACT Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin and BMP signaling systems in brown adipogenesis, we examined the effect of BMP7 in insulin receptor substrate 1 (IRS-1)-deficient brown preadipocytes, which exhibit a severe defect in differentiation. Treatment of these cells with BMP7 for 3 days prior to adipogenic induction restored differentiation and expression of brown adipogenic markers. The high level of adipogenic inhibitor preadipocyte factor 1 (Pref-1) in IRS-1-null cells was markedly reduced by 3 days of BMP7 treatment, and analysis of the 1.3-kb pref-1 promoter revealed 9 putative Smad binding elements (SBEs), suggesting that BMP7 could directly suppress Pref-1 expression, thereby allowing the initiation of the adipogenic program. Using a series of sequential deletion mutants of the pref-1 promoter linked to the luciferase gene and chromatin immunoprecipitation, we demonstrate that the promoter-proximal SBE (−192/−184) was critical in mediating BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance.

Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCβ2 axis

Blood ◽  
2009 ◽  
Vol 113 (1) ◽  
pp. 233-243 ◽  
Author(s):  
Yong-Sun Maeng ◽  
Hyun-Jung Choi ◽  
Ja-Young Kwon ◽  
Yong-Won Park ◽  
Kyu-Sil Choi ◽  
...  
Keyword(s):  
Postnatal Life ◽  
Protein Signaling ◽  
Vascular Networks ◽  
High Level Expression ◽  
Endothelial Progenitor ◽  
Hypoxic Conditions ◽  
High Level

Abstract Homing of endothelial progenitor cells (EPCs) to the neovascular zone is now considered to be an essential step in the formation of vascular networks during embryonic development and also for neovascularization in postnatal life. We report here the prominent role of the insulin-like growth factor 2 (IGF2)/IGF2 receptor (IGF2R) system in promoting EPC homing. With high-level expression of IGF2R in EPCs, IGF2-induced hypoxic conditions stimulated multiple steps of EPC homing in vitro and promoted both EPC recruitment and incorporation into the neovascular area, resulting in enhanced angiogenesis in vivo. Remarkably, all IGF2 actions were exerted predominantly through IGF2R-linked G(i) protein signaling and required intracellular Ca2+ mobilization induced by the β2 isoform of phospholipase C. Together, these findings indicate that locally generated IGF2 at either ischemic or tumor sites may contribute to postnatal vasculogenesis by augmenting the recruitment of EPCs. The utilization of the IGF2/IGF2R system may therefore be useful for the development of novel means to treat angiogenesis-dependent diseases.

Temperature Affects the Hydroxyapatite Crystal Arrangement on Silk Fibroin Surfaces

2017 ◽  
Vol 25 (9) ◽  
pp. 689-694
Author(s):  
Rui Zou ◽  
Qin Zhou ◽  
Qida Liu ◽  
Quanli Li ◽  
Zhiqing Chen ◽  
...  
Keyword(s):  
Particle Size ◽  
Silk Fibroin ◽  
Crystal Size ◽  
Crystal Nucleation ◽  
Deposition Pattern ◽  
Normal Bone ◽  
Bone Replacement ◽  
Coprecipitation Process ◽  
Hydroxyapatite Crystal ◽  
Crystal Arrangement

A hydroxyapatite (HAP)/silk fibroin (SF) bone-like biomaterial was fabricated through a coprecipitation process using stepped temperatures. We evaluated the effect of increasing temperatures on hydroxyapatite crystal arrangement on a silk fibroin surface. We found that the HAP crystal particles self-assembled on the silk fibroin surface. Further we found that with rising temperature the HAP crystal c-axis became progressively more parallel to the long axis of the silk fibroin. This deposition pattern is similar to that seen with HAP and collagen assembly in normal bone. Based on the XRD, SEM, and TEM results, we conclude that higher temperatures promote crystal nucleation resulting in an increase in both HAP crystal size and HAP/SF particle size. These data support the use of HAP/SF bone-like biomaterials for bone replacement and regeneration.

Micron-sized spinel crystals in high level waste glass compositions: Determination of crystal size and crystal fraction

2019 ◽  
Vol 514 ◽  
pp. 196-207
Author(s):  
C.E. Lonergan ◽  
K. Akinloye-Brown ◽  
J. Rice ◽  
V. Gervasio ◽  
N. Canfield ◽  
...  
Keyword(s):  
Crystal Size ◽  
Waste Glass ◽  
High Level Waste ◽  
Crystal Fraction ◽  
High Level ◽  
Glass Compositions
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