Overexpression of FGF2 delays the progression of osteonecrosis of the femoral head activating the PI3K/Akt signaling pathway.

BACKGROUND: The purpose of the current study was to explore the role and underlying mechanism of FGF-2 in dexamethasone (DEX)-induced apoptosis in MC3T3-E1 cells. METHODS: GSE21727 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. MC3T3-E1 cells were exposed to DEX at different concentrations (0, 10-8, 10-7, 10-6, 10-5 and 10-4 mol/L), and cell viability, flow cytometry and TUNEL assay were used to detect cell proliferation and apoptosis. An FGF-2-pcDNA3 plasmid (oe-FGF-2) was used to overexpress FGF-2, and western blotting was conducted to detect protein expression. RESULTS: We found that FGF-2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated FGF-2 gene and protein expression, inhibited viability and induced MC3T3-E1 cell apoptosis. Overexpression of FGF-2 reversed DEX-induced apoptosis in MC3T3-E1 cells. FGF-2-mediated anti-apoptosis was impaired by inactivating the PI3K/AKT pathway with LY294002. Moreover, overexpression of FGF2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model by regulation PI3K/Akt signaling pathway. CONCLUSION: In conclusion, FGF-2 is effective at inhibiting DEX-induced MC3T3-E1 cell apoptosis through regulating PI3K/Akt signaling pathway.

Systems Pharmacology-Based Precision Therapy and Drug Combination Discovery for Breast Cancer.

Breast cancer (BC) is a common disease and one of the main causes of death in females worldwide. In the omics era, researchers have used various high-throughput sequencing technologies to accumulate massive amounts of biomedical data and reveal an increasing number of disease-related mutations/genes. It is a major challenge to use these data effectively to find drugs that may protect human health. In this study, we combined the GeneRank algorithm and gene dependency network to propose a precision drug discovery strategy that can recommend drugs for individuals and screen existing drugs that could be used to treat different BC subtypes. We used this strategy to screen four BC subtype-specific drug combinations and verified the potential activity of combining gefitinib and irinotecan in triple-negative breast cancer (TNBC) through in vivo and in vitro experiments. The results of cell and animal experiments demonstrated that the combination of gefitinib and irinotecan can significantly inhibit the growth of TNBC tumour cells. The results also demonstrated that this systems pharmacology-based precision drug discovery strategy effectively identified important disease-related genes in individuals and special groups, which supports its efficiency, high reliability, and practical application value in drug discovery.

Feasibility of total en-bloc spondylectomy on L5 by a posterior-only approach: An autopsy study.

PURPOSE: To obtain a better understanding of the structures around L5 vertebra and provide some anatomical evidence of the feasibility of total en-bloc spondylectomy (TES) on L5 in a posterior-only approach. METHODS: 12 simulated TESs on L5 by a posterior-only approach were conducted on human cadavers. The distance between the traction point of L4 nerve root and the dural sac (Da), the anterior-posterior diameter of the vertebral body,(Va), the distance between the start point of L4 nerve root and the traction point of L5 nerve root (Dh) and the height of the vertebral body (Vh) were measured. Paired t-test and liner regression were performed to determine the difference and correlation between Da and Va, and between Dh and Vh. The risk of nerve roots or blood vessels damages, and the obstruction caused by iliac wings were evaluated. RESULTS: Liner correlations were found between Da and Va, and between Dh and Vh. The regression equations were Da = 0.6673Va + 11.28 and Dh = 1.009Vh + 1.003. There are statistical significant differences between Dh and Vh, and between Da and Va in those whose Va < 34.96 mm. Nerve roots or blood vessels damages and the obstruction caused by iliac wing were able to be avoided. CONCLUSIONS: If the patient has an anterior-posterior diameter of L5 vertebral body shorter than 34.96 mm, it is possible that the vertebral body can be taken out during TES in a posterior-only approach. Prevention of nerve roots or blood vessels damages, and the obstruction caused by iliac wings are difficulties of this procedure yet not insurmountable. TES on L5 by a posterior-only approach might a possible alternative in treating diseases like L5 vertebral body tumors.

Is unilateral pedicle screw fixation superior than bilateral pedicle screw fixation for lumbar degenerative diseases: a meta-analysis.

BACKGROUND: To investigate whether unilateral pedicle screw fixation is superior than bilateral pedicle screw fixation for lumbar degenerative diseases. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library up to August 2018 were searched. All the high-quality randomized controlled trials (RCTs) and prospective clinical controlled studies comparing the unilateral pedicle screw fixation and bilateral pedicle screw fixation for lumbar degenerative diseases were enrolled in this study. Fusion rate was the main outcome. Stata 12.0 was used for the meta-analysis. RESULTS: Twelve RCTs including 808 patients (unilateral pedicle screw fixation = 393, bilateral pedicle screw fixation = 415) were included in our meta-analysis. There was a significant difference between unilateral pedicle screw fixation and bilateral pedicle screw fixation in terms of the fusion rate (risk ratio (RR) = 0.96, 95%CI [0.92, 1.00], P = 0.073), visual analog scale (VAS) at final follow-up, Oswestry Disability Index (ODI), Japanese Orthopedic Association scores (JOA), short-form health survey (SF-36), and length of hospital stay. Compared with bilateral pedicle screw fixation, unilateral pedicle screw fixation was associated with a reduction of the total blood loss and operation time (P < 0.05). Unilateral pedicle screw fixation was associated with an increase of the cage migration than bilateral pedicle screw fixation (17.1% vs 7.1%, RR = 2.40, 95% CI = 1.17 to 4.93; P = 0.017). CONCLUSIONS: Unilateral pedicle screw fixation and bilateral pedicle screw fixation has similar fusion rate when treating for lumbar degenerative diseases. Our meta-analysis suggested that compared with bilateral pedicle screw fixation, unilateral pedicle screw fixation significantly reduced total blood loss and operation time for lumbar degenerative diseases. The use of unilateral pedicle screw for lumbar degenerative diseases increases the cage migration.

[Effects of water and nitrogen coupling under drip irrigation on tree growth and soil nitrogen content of Populus ×euramericana cv. 'Guariento'.] / 滴灌水氮耦合对欧美108æ¨æž—æœ¨ç”Ÿé•¿å’ŒåœŸå£¤æ°®ç´ çš„å½±å“.

By using surface drip irrigation, a field experiment including nine drip irrigation and fertigation treatments was carried out, with non-irrigation and non-fertilization as control (CK), to evaluate the integrative effects of water and nitrogen management on the increment of diameter, tree height, and stem volume, and the total nitrogen content in the 0-60 cm soil layer in the poplar (Populus ×euramericana cv. 'Guariento') plantations. There were three irrigation levels (irrigation was initiated when soil water potentials at 20 cm soil depth reached -75, -50 and -25 kPa) and three levels of nitrogen addition (150, 300 and 450 g·tree-1·a-1). Surface drip irrigation and fertigation treatments were applied in the gro-wing seasons of 2012 and 2013. The results showed that the combined treatments of water and nitrogen addition significantly increased growth and stem volume of the poplar plantation. In the first year of the experiment, the annual increment of stem volume was 11.54 m3·hm-2·a-1 in high water and high fertilizer treatment (soil water potentials of -25 kPa + nitrogen addition of 450 g·tree-1·a-1), which was 44.1% higher than that in the CK (8.01 m3·hm-2·a-1). In the second year, the annual increment of stem volume was 27.85 m3·hm-2·a-1 in medium water and high fertilizer treatment (soil water potentials of -50 kPa + nitrogen addition of 450 g·tree-1·a-1), being 36.0% higher than that in CK (20.48 m3·hm-2·a-1). The successive combined treatments signi-ficantly increased the total N content in the 0-20 cm soil layer, with total N content of each soil layer in the first and second year of the experiment being 12.3%-59.4% and 71.1%-81.1% higher than CK, respectively. The increments of diameter and tree height were significantly positively correlated with soil total N content. Nitrogen addition and the interactive effects of water and nitrogen addition significantly affected the diameter and height of trees and soil N content, while irrigation showed no significant effect. In conclusion, the combined drip irrigation and fertigation significantly increased growth and stem volume of the poplar plantation by promoting the soil fertility especially nitrogen availability in the topsoil.

Malvidin attenuates pain and inflammation in rats with osteoarthritis by suppressing NF-κB signaling pathway.

OBJECTIVE: Malvidin is one of the most widespread anthocyanidins which exhibits significant antioxidant and anti-inflammatory activity. The aim of this paper is to investigate the effects of Malvidin on osteoarthritis (OA). MATERIALS AND METHODS: We created an animal model of OA using Wistar rats administered by monosodium iodoacetate (MIA). Effects of Malvidin on hyperalgesia were evaluated by paw pressure tests and compression threshold test. Articular chondrocytes were isolated from the OA rats to detect the apoptotic chondrocytes using senescence-associated ß-galactosidase (SA-ß-gal) staining kit. The expression levels of pro-inflammatory cytokines and matrix metalloproteinase (MMPs) were assessed by western blot and qPCR. Luciferase assay was used to determine the impact of Malvidin on nuclear factor-kappa B (NF-κB) pathway. RESULTS: Malvidin treatment exhibited significant pain-relieving effects in OA rats and decreased the expression level of apoptotic marker SA-ß-gal in chondrocytes. We found that the upregulated expressions of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and MMPs induced by MIA in cartilage tissues were significantly reversed by Malvidin. Furthermore, Malvidin inhibited NF-κB pathway via an NF-κB inhibitor (IκBα)-independent manner through suppressing p65 nuclear transportation in vitro. CONCLUSIONS: Our findings suggest that Malvidin significantly attenuates the OA-induced pain and inflammation by inhibiting NF-κB signaling pathway and suppressing pro-inflammatory cytokine expression and chondrocyte apoptosis.

[Effects of fertilization method and nitrogen application rate on soil nitrogen vertical migration in a Populus xeuramericana cv. 'Guariento' plantation].

A field experiment was conducted to investigate the effects of fertilization methods, i.e., drip (DF) and furrow fertilization (GF), and nitrogen (N) application rates (25, 50, 75 g N · plant(-1) · time(-1)) on the dynamics of soil N vertical migration in a Populus x euramericana cv. 'Guariento' plantation. The results showed that soil NH4(+)-N and NO3(-)-N contents decreased with the increasing soil depth under different fertilization methods and N application rates. In the DF treatment, soil NH4(+)-N and NO3(-)-N were mainly concentrated in the 0-40 cm soil layer, and their contents ascended firstly and then descended, reaching their maximum values at the 5th day (211.1 mg · kg(-1)) and 10th day (128.8 mg · kg(-1)) after fertilization, respectively. In the GF treatment, soil NH4(+)-N and NO3(-)-N were mainly concentrated in the 0-20 cm layer, and the content of soil NO3(-)-N rose gradually and reached its maximum at the 20th day (175.7 mg · kg(-1)) after fertilization, while the NH4(+)-N content did not change significantly after fertilization. Overall, N fertilizer had an effect within 20 days in the DF treatment, and more than 20 days in the GF treatment. In the DF treatment, the content and migration depth of soil NH4(+)-N and NO3(-)-N increased with the N application rate. In the GF treatment, the NO3(-)-N content increased with the N application rate, but the NH4(+)-N content was not influenced. Under the DF treatment, the hydrolysis rate, nitrification rate and migration depth of urea were higher or larger than that under the GF treatment, and more N accumulated in deep soil as the N application rate increased. Considering the distribution characteristics of fine roots and soil N, DF would be a better fertilization method in P. xeuramericana cv. 'Guariento' plantation, since it could supply N to larger distribution area of fine roots. When the N application rate was 50 g · tree(-1) each time, nitrogen mainly distributed in the zone of fine roots and had no risk of deep leaching, consequently improving the fertilizer utilization efficiency.

Effects of Tanshinone IIA on osteogenic differentiation of mouse bone marrow mesenchymal stem cells.

Tanshinone IIA (TSA) is a lipophilic diterpene purified from the Chinese herb Danshen, which exhibits potent antioxidant and anti-inflammatory properties. Effect of TSA remains largely uninvestigated on the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs), which are widely used in cell-based therapy of bone diseases. In the present study, both ALP activity at day 7 and calcium content at day 24 were upregulated during the osteogenesis of mouse BM-MSCs treated with TSA (1 and 5 µM), demonstrating that it promoted the osteogenesis at both early and late stages. We found that TSA promoted osteogenesis and inhibited osteoclastogenesis, evident by RT-PCR analysis of osteogenic marker gene expressions. However, osteogenesis was inhibited by TSA at 20 µM. We further revealed that TSA (1 and 5 µM) upregulated BMP and Wnt signaling. Co-treatment with Wnt inhibitor DKK-1 or BMP inhibitor noggin significantly decreased the TSA-promoted osteogenesis, indicating that upregulation of BMP and Wnt signaling plays a significant role and contributes to the TSA-promoted osteogenesis. Of clinical interest, our study suggests TSA as a promising therapeutic strategy during implantation of BM-MSCs for a more effective treatment of bone diseases.