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1.
Sci Adv ; 10(14): eadk5229, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38569034

ABSTRACT

The origin of the cosmic magnetic field remains an unsolved mystery, relying not only on specific dynamo processes but also on the seed field to be amplified. Recently, the diffuse radio emission and Faraday rotation observations reveal that there has been a microgauss-level magnetic field in intracluster medium in the early universe, which places strong constraints on the strength of the initial field and implies the underlying kinetic effects; the commonly believed Biermann battery can only provide extremely weak seed of 10-21 G. Here, we present evidence for the spontaneous Weibel-type magnetogenesis in laser-produced weakly collisional plasma with the three-dimensional synchronous proton radiography, where the distribution anisotropy directly arises from the temperature gradient, even without the commonly considered interpenetrating plasmas or shear flows. This field can achieve sufficient strength and is sensitive to Coulomb collision. Our results demonstrate the importance of kinetics in magnetogenesis in weakly collisional astrophysical scenarios.

2.
Animals (Basel) ; 14(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38672293

ABSTRACT

Identifying genetic markers of economically valuable traits has practical benefits for the meat goat industry. To better understand the genomic variations influencing body conformation traits, a genome-wide association study was performed on Tashi goats, an indigenous Chinese goat breed. A total of 155 Tashi goats were phenotyped for eight body conformation traits: body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Then, 100 Tashi goats were randomly selected for whole-genome sequencing and genotyped. We obtained 1676.4 Gb of raw data with an average sequencing depth of 6.2X. Clean reads were aligned to the ARS1.2 reference genome, and 11,257,923 single nucleotide polymorphisms (SNPs) were identified. The structure analysis showed that these Tashi goats were almost not genetically related. The 109, 20, 52, 14, 62, 51, 70, and 7 SNPs were significantly associated with body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Within the ±500 kb region of significant SNPs, 183 genes were annotated. The most significantly enriched KEGG pathway was "olfactory transduction", and the most significantly enriched gene ontology (GO) terms were "cellular process", "cellular anatomical entity", and "molecular transducer activity". Interestingly, we found several SNPs on chromosomes 10 and 11 that have been identified multiple times for all eight body conformation traits located in two fragments (114 kb and 1.03 Mb). In chr.10:25988403-26102739, the six SNPs were tightly linked, the TACTAG genotype was the highest at 91.8%, and the FNTB (Farnesyltransferase, CAAX Box Beta) and CHURC1 (Churchill Domain Containing 1) genes were located. In chr.11:88216493-89250659, ten SNPs were identified with several dependent linkage disequilibrium (LD) blocks, and seven related genes were annotated, but no significant SNP was located in them. Our results provide valuable biological information for improving growth performance with practical applications for genomic selection in goats.

3.
ACS Omega ; 9(2): 2088-2103, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38250373

ABSTRACT

To explore the sedimentary environment and the background of the source area of organic-rich shales in the Wufeng-Longmaxi Formations in the northern Sichuan Basin, samples from Well XX1 in the area were subjected to geochemical testing and analysis of organic carbon content, trace elements, and rare earth elements (REEs). The results show that the total content of REE (ΣREE) of the shale in the Wufeng-Longmaxi Formations varied from 183.08 to 234.66 µg/g with an average of 212.59 µg/g, which is significantly higher than the content of the North American shale composite. The fluctuations in the total amount of REEs in the shale of the Wufeng-Longmaxi Formations reflect certain differences in the geochemical conditions of the Upper Ordovician-Lower Silurian shale. The ratios of LREE/HREE, LaN/YbN, LaN/SmN, and GdN/YbN and the distribution of normalized REE patterns indicate that the source supply or sedimentary structural background may have changed during the shale deposition period of the Wufeng Formation, while the shale deposition period of the Longmaxi Formation may be in a relatively stable source supply and sedimentary structural background. There is no significant correlation between δCe and ΣREE, and the obviously negative Eu abnormity and the weak Ce abnormity indicated that the diagenesis had a limited impact on REEs. Geochemical parameters such as values of ∑REE, δEu, δCe, Ceanom, and LaN/YbN indicate that the climate during the Wufeng-Longmaxi Formation shale deposition period was warm and humid, and the shale was deposited mainly in the suboxic-anoxic water environment. The deposition rate was stable and slow, providing good conditions for the production and preservation of organic matter. At the same time, this shows that the water environment of Wufeng Formation is more anoxic and reductive than that of Longmaxi Formation, which is more conducive to the preservation of organic matter. The correlation between ΣREE and the content of Sc, Ti, Cr, Co, Zr, Nb, Th, Hf, Ta, and other elements indicates that the sources of REEs in the shale of Wufeng and Longmaxi Formations in the study area are similar, mainly terrestrial clasts, and some may come from the sea. The REE distribution pattern shows that the shale provenance of the Wufeng-Longmaxi Formations mainly comes from the upper crust. The La/Yb-∑REE diagram shows that the sediment-parent rocks are mainly early sedimentary rocks and these sediment-parent rocks have granite provenance characteristics. Compared to La/Yb, LREE/HREE, LaN/YbN, and other REE characteristic parameters, it is inferred that the tectonic background of the study area is dominated by passive continental margin.

4.
Comput Methods Biomech Biomed Engin ; 26(14): 1761-1771, 2023.
Article in English | MEDLINE | ID: mdl-37902439

ABSTRACT

In order to understand the distribution of streaming potentials in cartilage pores, this paper established finite element model to analyze. The results showed that the streaming potential in cartilage micro-pores increased along the axis. The electric potential in 5 µm straight micro-pore was about 50 µV, and the electric potential of curved bifurcation model was about 30 µV. The pressure and Zeta potential had a linear growth relationship with the streaming potential. The streaming potential decreased with the increase of ion concentration until ion concentration was saturated. These results could provide a theoretical basis for cartilage research.


Subject(s)
Cartilage, Articular , Finite Element Analysis , Stress, Mechanical
6.
PLoS One ; 18(5): e0270614, 2023.
Article in English | MEDLINE | ID: mdl-37141336

ABSTRACT

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in isolated adipocytes from Zongdihua pigs. We aimed to identify biochemical processes affecting meat quality using molecular tools to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were over-expressed from recombinant plasmids. Sequence analysis of the cloned genes indicated that FABP1 encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane regions. The basal levels of FABP1 and FAS expression in pig tissues were 3-3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) over-expression of FAS resulted in significantly increased expression of COL3A1 (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) over-expression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P< 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, FAS enhanced FABP1 expression resulting in increased collagen accumulation and this preliminarily suggested that FAS and FABP1 can serve as fat-related candidate genes and provide a theoretical basis for the study of fat deposition in Zongdihua pigs.


Subject(s)
Fatty Acids , Protein-Lysine 6-Oxidase , Swine , Animals , Fatty Acids/metabolism , Protein-Lysine 6-Oxidase/genetics , Adipocytes/metabolism , Collagen/metabolism , Fatty Acid-Binding Proteins/genetics , Fatty Acid Synthases/metabolism
7.
Animals (Basel) ; 12(19)2022 Sep 26.
Article in English | MEDLINE | ID: mdl-36230312

ABSTRACT

The purpose of this study was to analyze the transcriptome of MyoD1 gene knockout MDBK cells (bovine kidney cells) using high-throughput sequencing. For the first time, CRISPR/CAS9 technology was used to construct a MyoD1 knockout in MDBK cells and transcriptome sequence analysis was used to examine MyoD1-related target gene expression. Transcriptome sequencing indicated the presence of 723 differentially expressed genes (DEGs) by comparing wild type and MyoD1 knockout MDBK cells and included 178 upregulated and 72 downregulated genes. The DEGs are mainly enriched in Pl-3-kinase and AKT, p53 signaling pathways. Quantitative RT-PCR confirmed that PDE1B, ADAMTS1, DPT, and CCND2 were highly expressed in the leg muscle, longissimus dorsi, and shoulder of Guanling cattle, and CCND2 was inhibited after MyoD1 knockout, suggesting it may be a key downstream gene of MyoD1 and associated with muscle formation and differentiation in Guanling cattle. This provides experimental data for subsequent studies on the regulatory mechanisms of muscle differentiation in Guanling cattle.

8.
Mol Med Rep ; 26(4)2022 Oct.
Article in English | MEDLINE | ID: mdl-35920186

ABSTRACT

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Fig. 2C were strikingly similar to data that had appeared in different form in another article by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 2281­2289, 2017; DOI: 10.3892/mmr.2017.6841].

9.
Int J Mol Med ; 44(2): 630-642, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31198977

ABSTRACT

Osteoarthritis (OA) is a common and troublesome disease among the elderly, and is characterized by extracellular matrix (ECM) degradation. The function of the long non­coding RNA X­inactive­specific transcript (XIST) and its working mechanism in ECM degradation remains unclear. In the present study, XIST was revealed to be upregulated in OA specimens and in articular chondrocytes (ACs) derived from OA tissue (AC/OA) and interleukin­1ß (IL­1ß)­treated ACs. Loss­of­function experiments demonstrated that downregulation of XIST suppressed the degradation of the ECM in AC/OA and AC/IL­1ß­5.0 cells. Furthermore, XIST, matrix metalloproteinase 13 (MMP­13) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) were identified as targets of microRNA (miR)­1277­5p, and the reciprocal inhibitive effect between XIST and miR­1277­5p was elucidated. Furthermore, the role of XIST in ECM degradation was confirmed to be functioning as a competing endogenous RNA (ceRNA) of miR­1277­5p. Finally, the protective effect of the downregulation of XIST on ECM degradation was verified in an OA rat model. In conclusion, the present study suggests that XIST promotes MMP­13 and ADAMTS5 expression, indicating ECM degradation, by functioning as a ceRNA of miR­1277­5p in OA. The present study proposed a novel potential target with a new working mechanism in molecular treating of OA.


Subject(s)
Extracellular Matrix/genetics , Gene Expression Regulation , MicroRNAs/genetics , Osteoarthritis/genetics , RNA, Long Noncoding/genetics , Animals , Cell Line , Extracellular Matrix/pathology , Female , Humans , Male , Middle Aged , Osteoarthritis/pathology , Rats
10.
Biosci Rep ; 39(1)2019 01 31.
Article in English | MEDLINE | ID: mdl-30455395

ABSTRACT

OBJECTIVE: To study the effects of single-nucleotide polymorphisms of the OPRM1 and ABCB1 genes on the analgesic effect and consumption of sufentanil after thoracoscopic-assisted radical resection of lung cancer. METHODS: A total of 225 Chinese Han nationality patients undergoing thoracoscopic-assisted radical resection of lung cancer were enrolled in the present study. Among them, 132 were males (58.67%) and 93 (41.33%) were females having American Society of Anesthesiologists statuses classified as grades I or II. The rs1799971, rs563649 and rs1323040 genotypes of the OPRM1 gene and rs2032582, rs1045642 and rs1128503 genotypes of the ABCB1 gene were detected by Sanger sequencing. The state anxiety index and pressure pain threshold were assessed preoperatively. Sufentanil was administered intravenously to maintain anesthesia. The doses and side effects of sufentanil consumed 6 h (T1), 24 h (T2) and 48 h (T3) after surgery were recorded. RESULTS: The sufentanil doses at T1, T2 and T3 were significantly higher in radical-operation lung cancer patients with mutant homozygous rs1799971 and rs1323040 loci in the OPRM1 gene and rs2032582 and rs1128503 loci in the ABCB1 gene. The doses of sufentanil consumed by mutant heterozygous lung cancer patients at T1, T2 and T3 were significantly higher than those consumed by patients without mutations, and the differences were statistically significant (P<0.05). There was no significant difference in sufentanil doses consumed by lung cancer patients with mutant homozygous, mutant heterozygous and wild-type rs563649 locus of the OPRM1 gene and rs1045642 locus of the ABCB1 gene at T1, T2 and T3 (P>0.05). There was no significant difference in the visual analog scale scores at T1, T2 and T3 for different genotypes of OPRM1 and ABCB1 genes in lung cancer patients (P>0.05). No significant difference was found between the adverse reactions of OPRM1 and ABCB1 genotypes in patients undergoing radical resection of lung cancer (P>0.05). CONCLUSION: The rs1799971 and rs1323040 polymorphisms of the OPRM1 gene and rs2032582 and rs1128503 polymorphisms of the ABCB1 gene are related to the analgesic effect and consumed dose of sufentanil in Chinese Han patients undergoing radical operation of lung cancer.


Subject(s)
Analgesics, Opioid/therapeutic use , Lung Neoplasms/surgery , Pain/prevention & control , Polymorphism, Single Nucleotide , Receptors, Opioid, mu/genetics , Sufentanil/therapeutic use , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Analgesics, Opioid/pharmacokinetics , Asian People , Base Sequence , Drug Administration Schedule , Drug Dosage Calculations , Female , Gene Expression , Genotype , Heterozygote , Homozygote , Humans , Lung Neoplasms/ethnology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Pain/physiopathology , Pain Measurement , Sufentanil/pharmacokinetics
11.
Mol Med Rep ; 16(2): 2281-2289, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28656198

ABSTRACT

MicroRNAs (miRNAs) are a group of non-protein­coding, short single-stranded RNAs, which are considered as promising molecular markers and therapeutic targets in several cancers. The present study explored the expression patterns and functional roles of miR­202 in non­small cell lung cancer (NSCLC). The expression levels of miR­202 were determined in NSCLC tissues and cell lines using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The functional impact of miR­202 overexpression on NSCLC cell viability, migration and invasion were evaluated using Cell Counting Kit­8 reagent and Transwell migration and invasion assays, respectively. The molecular mechanism underlying the tumor suppressive roles of miR­202 on NSCLC was examined using bioinformatics analysis, luciferase reporter assay, RT­qPCR and western blot analysis. In addition, signal transducer and activator of transcription (STAT) 3 was overexpressed to investigate the impact on miR­202­mediated tumor suppression in NSCLC. The results indicated that miR­202 was downregulated in NSCLC tissues and cell lines, and was associated with tumor node metastasis stage and lymph node metastasis. Exogenous miR­202 expression reduced NSCLC cell viability, migration and invasion. Furthermore, STAT3 was identified as a direct target gene of miR­202 in NSCLC. STAT3 overexpression improved miR­202­impaired cell viability, migration and invasion. In conclusion, the present study revealed novel anticancer effects induced by miR­202 upregulation in NSCLC, and indicated that STAT3 may be a molecular target of miR­202.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , MicroRNAs/metabolism , STAT3 Transcription Factor/metabolism , 3' Untranslated Regions , A549 Cells , Aged , Antagomirs/metabolism , Base Sequence , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Movement , Cell Survival , Down-Regulation , Female , Humans , Lung Neoplasms/metabolism , Lymphatic Metastasis , Male , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Middle Aged , Neoplasm Staging , STAT3 Transcription Factor/chemistry , STAT3 Transcription Factor/genetics , Sequence Alignment
12.
Int J Clin Exp Med ; 8(5): 6762-72, 2015.
Article in English | MEDLINE | ID: mdl-26221214

ABSTRACT

AIM: To document the clinicopathological characteristics and analyze the possible reasons for misdiagnosis or missed diagnosis of hepatoid adenocarcinoma of the stomach (HAS), using data from a single center. METHODS: We retrospectively analyzed 19 patients initially diagnosed as HAS and 7 patients initially diagnosed as common gastric cancer with high levels of serum α-fetoprotein (AFP). All had undergone surgical treatment, except 3 patients only had biopsies at our hospital. Immunohistochemistry for AFP and Hepatocyte antigen was performed. Final diagnosis for these 26 patients were made after HE and immunohistochemistry slides reviewed by 2 experienced pathologists. Prognostic factors were determined by univariate analysis. RESULTS: Nineteen cases were confirmed to be HAS. A total of 4 out of 19 cases initially diagnosed as HAS and 4 out of 7 cases initially diagnosed as common gastric adenocarcinoma were misdiagnosed/missed diagnosed, thus, the misdiagnosis/missed diagnosis rate was 30.8% (8/26). The incidence of HAS among gastric cancer in our center was 0.19% (19/9915). Sixteen (84.2%) patients showed T stages greater than T2, 12 (70.6%) patients had positive lymph nodes in 17 available patients and 3 (15.8%) of the patients with tumors presented liver metastasis at the time of diagnosis. Histologically, cytoplasmic staining types included 10 cases of eosinophilic, 1 case of clear, 5 cases of clear mixed with eosinophilic and 3 cases of basophilic. Fourteen (73.7%) patients expressed AFP, whereas only 6 (31.6%) were hepatocyte-positive. Univariate analysis showed that N stage (HR 2.429, P=0.007) and tumor AFP expression (HR 0.428, P=0.036) were significantly associated with disease-free survival. The median overall survival time was 12.0 months, and the median disease-free survival time was 7.0 months. Four (80%) of 5 N0 patients and 2 (50%) of 4 N1 patients survived without progression, but no N2-3 patients survived. CONCLUSION: HAS remains easily being misdiagnosed/missed diagnosed based on a pathological examination, probably because the condition is rare and has various cytoplasmic types. Although the survival rate for HAS is poor, a curative effect may be achieved for N0 or N1 cases.

13.
Oncol Lett ; 6(5): 1363-1369, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24179525

ABSTRACT

The aim of the present study was to investigate the expression profile and prognostic significance of uncoordinated 5 homolog 4 (UNC5H4) in patients with lung cancer and to evaluate whether UNC5H4 expression may serve as an index for radiosensitivity. UNC5H4 and p53 expression levels were detected by immunohistochemistry, apoptosis was determined by a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and caspase 3 activation was determined by western blotting. The results showed that UNC5H4 expression was largely located in the membrane of the normal bronchial epithelium, but absent in the membranous regions or ectopic cytoplasm of 80/130 (61.5%) non-small cell lung cancer (NSCLC) tissue samples. Abnormal UNC5H4 expression was demonstrated to correlate with the degree of differentiation (P=0.015), TNM staging (P=0.037). Cytoplasmic UNC5H4 expression was shown to correlate negatively with p53 mutant type (mt) expression (r=-0.270; P=0.002) and positively with the apoptotic index (r=0.254; P=0.004). The statistical analyses indicated that the prognosis of patients with normal UNC5H4 expression was improved compared with that of patients with abnormal UNC5H4 expression, however, no significant difference was identified (P=0.125). Exposure of NSCLC tissue samples to X-radiation increased UNC5H4 expression and caspase 3 activity significantly, irrespective of p53 mutation status. In conclusion, these results indicate that X-rays induce apoptosis via the p53 pathway, and when this pathway is compromised, an additional pathway is utilized.

14.
Zhonghua Wai Ke Za Zhi ; 43(23): 1528-32, 2005 Dec 01.
Article in Chinese | MEDLINE | ID: mdl-16412291

ABSTRACT

OBJECTIVE: To evaluate the status of promoter hypermethylation of Ras association domain family protein 1A (RASSF1A), hypermethylated in cancer 1 (HIC1) and p73 genes in hepatocellular carcinoma (HCC) and to explore the correlation with clinicopathological features. METHODS: Forty cases of HCC and their corresponding non-tumor liver tissues, other 2 cases of healthy donor livers were detected using methylation specific polymorphism chain reaction (MSP) method. RESULTS: The frequency of promoter hypermethylation of RASSF1A showed 90.0% and 72.5% in tumor and corresponding non-tumor tissues respectively, and there was significant difference between them (P < 0.05). The frequency of promoter hypermethylation of HIC1 showed 77.5% and 70.0% in tumor and corresponding non-tumor tissues respectively. The frequency of hypermethylation of HIC1 in non-tumor liver tissues showed significant correlation between younger and older patients. The frequency of promoter hypermethylation of p73 showed 5.0% in tumor tissues. However, none of hypermethylation of the gene was detected in corresponding non-tumor liver tissues. There was none of hypermethylation of the three genes showed in two cases of healthy donor livers. CONCLUSION: Promoter hypermethylation of RASSF1A and HIC1 genes are common event in HCC and play an important role in the pathogenesis and may be used to develop novel diagnostic and therapeutic approaches for HCC in the future.


Subject(s)
Carcinoma, Hepatocellular/genetics , DNA Methylation , DNA-Binding Proteins/genetics , Kruppel-Like Transcription Factors/genetics , Liver Neoplasms/genetics , Nuclear Proteins/genetics , Promoter Regions, Genetic/genetics , Tumor Suppressor Proteins/genetics , Adult , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Tumor Protein p73
15.
Article in Chinese | MEDLINE | ID: mdl-12181780

ABSTRACT

OBJECTIVE: To study the effect of two cytokines, basic fibrolast growth factor(bFGF) and insulin-like growth factor-I(IGF-I), on cell proliferation in chondrocytes of adult rabbits. METHODS: The primary chondrocytes of adult rabbits were harvested and cultured with bFGF and IGF-I at different concentrations, respectively, as well as with the mixture of the two cytokines; the quantity of cultured chondrocytes was detected by MTT assay at the 24th, 48th and 72nd hours; and the final fold increase of different groups was measured by cell count for the 3rd passage; and the proliferation index of the groups was recorded by flowing cytometer on the 14th day. RESULTS: 1. The cultured chondrocytes with either bFGF, IGF-I or their mixture were significantly more than that of control group at the 24th, 48th and 72th hours (P < 0.01). 2. After the 3rd passage, the final folds of proliferation were significantly higher in the groups with cytokines than in the control group (P < 0.01); and the final fold with the mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P < 0.01). 3. The proliferation index was significantly higher in the groups with cytokines than in the control group (P < 0.01); the proliferation index with the mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P < 0.05); besides, proliferation index was higher when cytokine was applied twice than once (P < 0.05); besides, proliferation index was higher when cytokine was applied twice than once (P < 0.05). CONCLUSION: bFGF and IGF-I could promote chondrocytes proliferation of adult rabbits obviously and they are synergistic in cell proliferation.


Subject(s)
Cartilage, Articular/cytology , Chondrocytes/drug effects , Fibroblast Growth Factor 2/pharmacology , Insulin-Like Growth Factor I/pharmacology , Animals , Cell Division/drug effects , Cells, Cultured , Chondrocytes/cytology , Drug Synergism , Rabbits
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