scholarly journals Autophagy in Femoral Head Necrosis of Broilers Bone Metabolism Parameters and Autophagy-Related Gene Expression in Femoral Head Necrosis Induced by Glucocorticoid in Broilers

2021 ◽  
Vol 8 ◽  
Author(s):  
Kaiyi Pang ◽  
Shujie Wang ◽  
Meng Li ◽  
Zhenlei Zhou
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Femoral Head ◽  
Bone Quality ◽  
Density Lipoprotein ◽  
Femoral Head Necrosis ◽  
Blood Levels ◽  
Histopathological Analysis ◽  
Type I ◽  
Related Gene

Objectives: In this study, the influence of methylprednisolone (MP) and 3-methyladenine (3-MA) on chondrocyte autophagy and bone quality were determined to investigate the mechanisms of femoral head necrosis in broilers.Methods: Chickens were divided into four groups: control, MP, 3-MA, and 3-MA+MP groups. Blood and bone samples were collected for biochemistry assay and bone quality determination. Cartilage was separated from the femoral head for histopathological analysis and gene expression detection.Results: The results indicated that MP treatment significantly affected blood levels of alkaline phosphatase, high-density lipoprotein, calcium, phosphorus, bone alkaline phosphatase, and osteocalcin in broilers. Additionally, MP treatment significantly increased blood levels of cholesterol, low-density lipoprotein, triglyceride, carboxy-terminal telopeptide of type-I collagen, and tartrate-resistant acid phosphatase 5. MP treatment also significantly decreased the levels of bone parameters compared with these values in controls, inhibited the expression of collagen-2, aggrecan, and mammalian target of rapamycin, and increased the expression of beclin1 and microtubule-associated protein 1 light chain 3, hypoxia-inducible factor 1 alpha, phosphoinositide 3-kinase, protein kinase B and autophagy-related gene 5 of the femoral head. Furthermore, following co-treatment with 3-MA and MP, 3-MA mitigated the effects of MP.Conclusions: Our findings demonstrated that autophagy may be involved in the pathogenesis of femoral head necrosis induced by MP in broilers, and this study provides new treatment and prevention ideas for femoral head necrosis caused by glucocorticoids.

The influence of titanium surfaces treated by alkalis on macrophage and osteoblast-like cell adhesion and gene expression in vitro

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 81378-81387 ◽  
Author(s):  
Ting Ma ◽  
Xi-Yuan Ge ◽  
Sheng-Nan Jia ◽  
Xi Jiang ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Cell Adhesion ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Related Gene ◽  
Titanium Surfaces

The effect of alkali-treated titanium surfaces on inflammation-related gene expression of macrophages and alkaline phosphatase activity of osteoblast-like cells.

Impact of mutant IDH (mIDH) inhibition on DNA hydroxymethylation, tumor cell function, and tumor immune microenvironment (TIME) in resected mIDH1 lower-grade glioma (LGG).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2008-2008
Author(s):  
Min Lu ◽  
Timothy Francis Cloughesy ◽  
Patrick Y. Wen ◽  
Ania Tassinari ◽  
Sung Choe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Cell ◽  
Antigen Presentation ◽  
Post Treatment ◽  
Type I ◽  
Interferon Signaling ◽  
Related Gene ◽  
Ki 67 ◽  
Dual Inhibitor ◽  
Upper Limit

2008 Background: Somatic mutations in IDH1 and IDH2 occur in ̃80% and ̃4% of LGGs, respectively, promoting tumorigenesis via increased levels of the oncometabolite D-2-hydroxyglutarate (2-HG). Vorasidenib (VOR; AG-881) is an oral, brain-penetrant, dual inhibitor of mIDH1/2; ivosidenib (IVO; AG-120) is a first-in-class oral inhibitor of mIDH1. In this ongoing perioperative study, treatment with IVO/VOR reduced 2-HG levels in resected tumors vs untreated control tumors in patients (pts) with LGG (NCT03343197; Mellinghoff SNO 2019). We assessed the biological impact of 2-HG suppression on tumors and TIME. Methods: Pts (n = 49) with recurrent, non-enhancing, mIDH1-R132H LGG eligible for resection were randomized to IVO (500 mg QD/250 mg BID), VOR (10/50 mg QD), or no treatment, for 4 weeks preoperatively. Tumor tissue samples collected at surgery were assessed in genomic (n = 42), transcriptomic (n = 42), and immunohistochemistry (IHC; n = 43) analyses. Unpaired t-test was used for statistical comparisons. Results: Optimal 2-HG suppression (post-treatment 2-HG below the upper limit of 2-HG levels in a reference set of 15 wild-type [wt] IDH samples) was observed in 23 of 40 pts, including 9 (90%) pts receiving VOR 50 mg QD and 6 (50%) receiving IVO 500 mg QD. Of samples with valid biomarker data, those with optimal 2-HG suppression (n = 21) showed upregulation of neural differentiation-related gene expression, but downregulation of stemness-related gene expression, vs those with suboptimal 2-HG suppression (post-treatment 2-HG above upper limit of wt IDH 2-HG levels; n = 17; p < 0.01). IHC analysis of the proliferation marker Ki-67 showed a ̃2-fold decrease in Ki-67–positive cells in samples with optimal 2-HG suppression (mean 2.7%; n = 22) vs those with suboptimal suppression (5.8%; n = 16; p < 0.05). Epigenetic analysis revealed a ̃2-fold increase in mean 5-hydroxymethylcytosine (5hmC) levels in samples with optimal (0.36%; n = 17) vs suboptimal 2-HG suppression (0.2%; n = 15; p < 0.05), suggesting reversal of TET2 inhibition. IHC analysis of TIME revealed increases in mean CD3+ and CD8+ tumor-infiltrating lymphocyte levels in samples with optimal (1.05% [CD3]/0.22% [CD8]; n = 22) vs suboptimal 2-HG suppression (0.44% [CD3]/0.07% [CD8]; n = 16; p < 0.05). Optimal 2-HG suppression was associated with upregulation of gene expression related to type I interferon signaling and antigen presentation (p < 0.01). Conclusions: These data suggest that both tumor-intrinsic and -extrinsic mechanisms underlie 2-HG suppression by VOR and IVO. VOR, and IVO to a lesser extent, increased 5hmC, promoted cellular differentiation, and inhibited tumor cell proliferation; both also increased T-cell infiltration, activated interferon signaling, and increased antigen presentation capability. These data support development of VOR in combination with immunotherapy. Clinical trial information: NCT03343197.

HDL promotes adiponectin gene expression via the CAMKK/CAMKIV pathway

2021 ◽  
Author(s):  
Toshihiro Kobayashi ◽  
Hitomi Imachi ◽  
Kensaku Fukunaga ◽  
Jingya Lyu ◽  
Seisuke Sato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Promoter Activity ◽  
Active Form ◽  
Specific Inhibitor ◽  
Density Lipoprotein ◽  
Dominant Negative ◽  
Activation Mechanism ◽  
Dominant Negative Mutant ◽  
Type I

Adiponectin (APN) is an adipokine that protects against diabetes and atherosclerosis. High-density lipoprotein (HDL) mediates reverse cholesterol transport, which also protects against atherosclerosis. In this process, the human homolog of the B class type I scavenger receptor (SR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. The level of circulating adiponectin is positively correlated with the serum level of HDL-cholesterol. In this study, we investigated whether HDL stimulates the gene expression of adiponectin through the Ca²+/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) cascade. Adiponectin expression was examined using real-time PCR and western blot analysis in 3T3-L1 cells incubated with HDL. CaMKIV activity was assessed by detection of activation loop phosphorylation (at Thr196 residue), and the effect of the constitutively active form, CaMKIVc, on adiponectin promoter activity was investigated. Our results showed that HDL stimulated APN gene expression via hSR-BI/CLA-1. Furthermore, we explored the signaling pathways by which HDL stimulated APN expression in 3T3-L1 cells. The stimulation of APN gene expression by HDL appears to be mediated by CaMKK, as STO-609, a specific inhibitor of CaMKK2, prevents this effect. We revealed that CaMKIVc increased APN gene transcriptional activity, and the CaMKIV dominant negative mutant blocked the effect of HDL on APN promoter activity. Finally, knockdown of hSR-BI/CLA-1 also cancelled the effect of HDL on APN gene expression. These results suggest that HDL has important role to improve the function of adipocytes by activating hSR-BI/CLA-1 and CaMKK/CaMKIV pathway is conceivable as one of the signaling pathways of this activation mechanism.

Contribution to the Diagnosis of Idiopathic Femoral Head Necrosis by Scintigraphy with 99mTc-MDP Assessed Quantitatively by Computer

1983 ◽  
Vol 22 (05) ◽  
pp. 232-236 ◽  
Author(s):  
J. Pardo-Montaner ◽  
O. Caballero-Carpena
Keyword(s):  
Femoral Head ◽  
Gamma Camera ◽  
Lumbar Vertebra ◽  
Subjective Assessment ◽  
The Other ◽  
Femoral Head Necrosis ◽  
Control Group ◽  
Histopathological Analysis ◽  
Femoral Heads ◽  
Abnormal Uptake

The authors have studied by quantification the bone uptake of 99mTc-MDP in femoral head necrosis in order to evaluate in an objective manner conventional scintigraphy, and thus to increase the sensitiveness and efficacy of an exploration for an early diagnosis of these patients. Twenty cases of femoral necrosis have been studied, diagnosed in all cases by histopathological analysis; in twelve of them the process was unilateral and in the other eight bilateral. All explorations were carried out with 99mTc-MDP, a gamma camera and a PDP 11/40 computer for the quantitative study with the obtention of indices relating the activity between the femoral heads and, of these, to a normal vertebra. Quantification in the control group showed that the uptake of the nuclide was similar in both femoral heads and is lower than this in the vertebra. In all cases of unilateral necrosis the abnormal deviations of the indices relating the pathological head to the contralateral head and the lumbar vertebra were significant. In bilateral femoral head necrosis, an increase has been observed in all indices, although only the index relating the contralateral femoral head suspect of a lesion to vertebral activity was statistically significant. The proposed method for quantifying can be carried out easily and is very useful for diagnosing femoral necrosis since it improves the results of a subjective assessment of the scintigraphic image and can earlier detect the abnormal uptake of the lesion.

scholarly journals Hydroxysafflor Yellow A Promoted Bone Mineralization and Inhibited Bone Resorption Which Reversed Glucocorticoids-Induced Osteoporosis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Li Liu ◽  
Weiwei Tao ◽  
Wenjia Pan ◽  
Li Li ◽  
Qiong Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mineralization ◽  
Bone Collagen ◽  
Whole Body ◽  
Type I ◽  
Related Gene ◽  
Hydroxysafflor Yellow A ◽  
Zebrafish Model

Glucocorticoids intake is the most common cause of secondary osteoporosis. Clinical studies have shown that 50% patients develop glucocorticoids-induced osteoporosis (GCIOP) after taking glucocorticoids for more than 6 months. Hydroxysafflor yellow A (HYA) is one main active ingredient in Carthamus tinctorius L. Previous studies have shown that HYA promoted bone marrow mesenchymal stem cells to differentiate into osteoblasts which promoted bone formation. Therefore, we speculated that HYA has a therapeutic effect on GCIOP. However, there is no in vivo evidence about the anti-GCIOP effect of HYA. In this paper, the effect of HYA (0.1, 1.0, and 10.0 μM) on bone formation in normal zebrafish was investigated firstly. Secondly, the reversal effect of HYA on GCIOP was also evaluated by zebrafish model. It is demonstrated that HYA not only promoted bone formation in normal zebrafish (compared to Control group), but also reversed glucocorticoid induced bone loss (compared to Prednisolone group) according to the intervention of HYA in upregulating the area of mineralized bones (p < 0.01), increasing cumulative optical density (p < 0.01), promoting bone formation related gene expression (AKP, Type I, Runx2, OPG, and OCN, p < 0.01), inhibiting bone resorption related gene expression (TRACP, p < 0.01), and elevating whole-body trace mineral elements (Ca, P, K, Mg, Zn, and Fe) levels (p < 0.01). In conclusion, HYA had the potential to prevent and heal GCIOP by promoting bone mineralization, osteoblasts viability, and bone collagen expression and inhibiting bone resorption.

scholarly journals Enhanced p53 Levels Are Involved in the Reduced Mineralization Capacity of Osteoblasts Derived from Shwachman–Diamond Syndrome Subjects

2021 ◽  
Vol 22 (24) ◽  
pp. 13331
Author(s):  
Annalisa Frattini ◽  
Simona Bolamperti ◽  
Roberto Valli ◽  
Marco Cipolli ◽  
Rita Maria Pinto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Ribosome Biogenesis ◽  
Collagen Type ◽  
Bone Marrow Failure ◽  
Pancreatic Insufficiency ◽  
Collagen Type I ◽  
Type I ◽  
Protein Levels ◽  
Shwachman Diamond Syndrome

Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced SBDS gene expression and reduced/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs. Whole transcriptome analysis showed significant differences in the gene expression of SDS-OBs vs. H-OBs, particularly in the ossification pathway. SDS-OBs expressed lower levels of the main genes responsible for osteoblastogenesis. Of all downregulated genes, Western blot analyses confirmed lower levels of alkaline phosphatase and collagen type I in SDS-OBs than in H-OBs. Interestingly, SDS-OBs showed higher protein levels of p53, an inhibitor of osteogenesis, compared to H-OBs. Silencing of Tp53 was associated with higher collagen type I and alkaline phosphatase protein levels and an increase in SDS-OB mineralization capacity. In conclusion, our results show that the reduced capacity of SDS-OBs to mineralize is mediated, at least in part, by the high levels of p53 and highlight an important role of SBDS in osteoblast functions.

scholarly journals Cartilage Homeostasis Affects Femoral Head Necrosis Induced by Methylprednisolone in Broilers

2020 ◽  
Vol 21 (14) ◽  
pp. 4841 ◽  
Author(s):  
Yaling Yu ◽  
Shujie Wang ◽  
Zhenlei Zhou
Keyword(s):  
Femoral Head ◽  
Broiler Chickens ◽  
Large Scale ◽  
Critical Role ◽  
Femoral Head Necrosis ◽  
Control Group ◽  
Histopathological Analysis ◽  
Sterile Saline ◽  
Bone Parameters ◽  
Cartilage Homeostasis

(1) Background: Since the large-scale poultry industry has been established, femoral head necrosis (FHN) has always been a major leg disease in fast-growing broilers worldwide. Previous research suggested that cartilage homeostasis could be taken into consideration in the cause of FHN, but the evidence is insufficient. (2) Methods: One-day-old broiler chickens were randomly divided into three groups, 16 broilers per group. The birds in group L were injected intramuscularly with methylprednisolone (MP) twice a week for four weeks (12.5 mg·kg−1). The birds in group H were injected intramuscularly with MP (20 mg·kg−1·d−1) for 7 d (impulse treatment). The birds in group C were treated with sterile saline as a control group. Broilers were sacrificed at 42 and 56 d. Blood samples were collected from the jugular vein for ELISA and biochemical analysis. Bone samples, including femur, tibia, and humerus, were collected for histopathological analysis, bone parameters detection, and real-time quantitative PCR detection. (3) Results: The FHN broilers in group L and H both showed lower body weight (BW) and reduced bone parameters. In addition, the MP treatment resulted in reduced extracellular matrix (ECM) anabolism and enhanced ECM catabolism. Meanwhile, the autophagy and apoptosis of chondrocytes were enhanced, which led to the destruction of cartilage homeostasis. Moreover, the impulse MP injection increased the portion of birds with severer FHN, whereas the MP injection over a long period caused a more evident change in serum cytokine concentrations and bone metabolism indicators. (4) Conclusions: The imbalance of cartilage homeostasis may play a critical role in the development of FHN in broilers. FHN broilers induced by MP showed a more pronounced production of catabolic factors and suppressed the anabolic factors, which might activate the genes of the WNT signal pathway and hypoxia-inducible factors (HIFs), and then upregulate the transcription expression of ECM to restore homeostasis.

scholarly journals L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Qiongxian Yan ◽  
Haiou Tong ◽  
Shaoxun Tang ◽  
Zhiliang Tan ◽  
Xuefeng Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Fatty Acids ◽  
Body Weight ◽  
Small Intestine ◽  
Insulin Secretion ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Related Gene ◽  
Dietary Nutrients

L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight) per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters SLC7a1 and SLC7a9, neutral SLC1a5 and SLC16a10, and acidic SLC1a1 expression were upregulated. The expression of intestinal SGLT3 and GLUT5 responsible for carbohydrates uptake and GPR120 and FABP2 associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration.

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