The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family consists of 19 proteases. These enzymes are known to play important roles in development, angiogenesis and coagulation; dysregulation and mutation of these enzymes have been implicated in many disease processes, such as inflammation, cancer, arthritis and atherosclerosis. This review briefly summarizes the structural organization and functional roles of ADAMTSs in normal and pathological conditions, focusing on members that are known to be involved in the degradation of extracellular matrix and loss of cartilage in arthritis, including the aggrecanases (ADAMTS-4 and ADAMTS-5), ADAMTS-7 and ADAMTS-12, the latter two are associated with cartilage oligomeric matrix protein (COMP), a component of the cartilage extracellular matrix (ECM). We will discuss the expression pattern and the regulation of these metalloproteinases at multiple levels, including their interaction with substrates, induction by pro-inflammatory cytokines, protein processing, inhibition (e.g., TIMP-3, alpha-2-macroglobulin, GEP), and activation (e.g., syndecan-4, PACE-4).
ADAM Proteins ; antagonists & inhibitors ; chemistry ; genetics ; physiology ; Aggrecans ; metabolism ; Alternative Splicing ; Arthritis ; enzymology ; genetics ; Cartilage ; enzymology ; Endopeptidases ; genetics ; physiology ; Extracellular Matrix ; enzymology ; Humans ; Protein Structure, Tertiary

Objective: To study the effects of glycosaminoglycan from scallop skirt (SS-GAG) on the expression of vascular endothelial growth factor (VEGF) and the mechanism of anti-atherosclerosis action of SS-GAG. Methods: U937 cells were incubated with 80mg/L oxidized low density lipoprotein (ox-LDL) for 48h to establish a macrophage-derived foam cell model. In addition, U937 cells were divided into 6 groups: ①control group; ②ox-LDL group; ③ox-LDL+200mg/L SS-GAG group; ④ox-LDL+400 mg/L SS-GAG group; ⑤ox-LDL+800 mg/L SS-GAG group; ⑥ox-LDL +Heparin 100 mg/L group.After 48h's incubation, the concentration of VEGF in the medium was determined by ELISA. Results: The expression of VEGF in U937 foam cells was obviously higher than that of the control group. After treatment with heparin (100 mg/L) and SS-GAG of different concentrations (200mg/L, 400 mg/L, 800 mg/L), the expression of VEGF decreased obviously, especially in the ox-LDL+800 mg/L SS-GAG group (P＜0.01). Conclusion: The antiatherogenic effect of SS-GAG is probably due to its ability to inhibit VEGF expression.

MISA (MicroSAtelite) software was employed to screen SSRs in 68 787 contigs of Swertia mussotii transcriptome sequences. 5 610 SSRs were distributed in 5 099 contigs which accounted for 7.41% of 68 787 contigs. There are 220 kinds of SSR motifs existing in S. mussotii transcriptome. On average, SSRs occurred every 12.60 kb in length. In the SSRs, the tri-nucleotide repeat motif was the most abundant (45.99%), followed by the di-nucleotide (41.62%). AT/TA and AAT/TTA were the main types of motif in di-, tri-nucleotide repeats. The repeat numbers of SSRs which from S. mussotii transcriptome SSRs were mainly from 5 to 10 and motif length of them mostly ranged from 12 bp to 30 bp. A total of 30 651 contigs were annotated, and only 1 447 SSRs were occurred in protein-coding regions. In the six repeat motifs, tri-nucleotide repeats were the most abundant in coding regions (928). There are abundant SSRs in S. mussotii transcriptome with high frequency and various types, indicating their usefulness in theory. This research may lay the foundation for designing the targeted SSR primers and developing SSR molecular markers by mining the information of SSRs loci in S. mussotii transcriptome sequences data.
Data Mining ; Medicine, Tibetan Traditional ; Microsatellite Repeats ; Plants, Medicinal ; genetics ; Swertia ; genetics ; Transcriptome

Objective To explore the epidemiological characteristics and influencing factors of fall of elderly aged ≥ 60 years in Guangzhou from 2014 to 2018 ，so as to provide evidence for effective prevention and control measures． Methods Data on fall of the elderly was collected from the first diagno- sis in injury surveillance hospitals in Guangzhou from 2014 to 2018，and distribution description and epi- demiological analysis were adopted． Ｒesults 9 503 cases of fall of the elderly were reported in 5 injury surveillance hospitals，accounting for 49．41% of injuries in the elderly，and had occupied the first place in the cause of injury in 5 consecutive years． The sex ratio of men to women was 1 ∶ 1．67． Most of the patients had a primary or junior school degree，high rate in October-December，mainly occurred at home when doing leisure activities or life activities． The fall mainly led to injuries of head or lower extremities， contributed to contusion /bruise or fracture． And most of them were mild and moderate injury． Logistic re- gression showed that female，old age，high educational level，December to February，at home，walking， leisure activities and life activities were risk factors for falling among the elderly in Guangzhou ( all P ＜ 0．001) ． Conclusions Fall is the primary cause of injuries to the elderly in Guangzhou，especially the elderly female population． The targeted prevention and intervention measures should be developed ac- cording to their distribution characteristics．

OBJECTIVETo explore the expression of vascular endothelial growth factor (VEGF) and its receptors (flt-1 and flk-1) in the retina of retinopathy of prematurity (ROP), and its relation to the alteration of retinal blood vessels.

METHODSEighty-six newborn Sprague-Dawley rats were randomly divided into hyperoxia and air groups, then each group was further divided into 1, 3, 7 and 14 days subgroups. The rats in hyperoxia group inhaled 75% oxygen and ROP model was thus set up. These animals were sacrificed respectively after 1, 3, 7 and 14 days, then the retinal endothelial cells were marked by CD34 to observe the change of retinal blood vessels. The expression of VEGF, flt-1 and flk-1 in the retina was measured by immunohistochemistry.

RESULTSThe retinal capillary density index (RCDI) in control group increased as days went on (F = 21.589, P < 0.01, but it was the least on the 7th day in hyperoxia group, after the rats had been returned to air for 7 days, RCDI increased significantly (F = 67.885, P < 0.01); In the control group, the expression of VEGF and flk-1 was the strongest in the retina on the 7th day, the result had significant difference as compared with the 1st and 14th day (P < 0.05). The expression of VEGF and flk-1 on the 7th day in hyperoxia group was weaker than that of control group (P < 0.05). But on the 14th day in hyperoxia group, they were stronger than that of control (P < 0.05). The localization of the expression of flt-1 was changed when blood vessels altered, but there was no significant difference in expression intensity as a whole (P > 0.05).

CONCLUSIONWhen the premature retina was exposed to hyperoxia, the expression of VEGF and flk-1 was reduced, and retinal blood vessels were also decreased; but the expression of VEGF and flk-1 was stronger in retina when premature rats were exposed to relative hypoxia, and the retinal blood vessels also increased significantly. It is concluded that VEGF and flk-1 may play important roles in the development of retinal blood vessels and its change in ROP. However, flt-1 has less effect compared with flk-1.

Animals ; Animals, Newborn ; Disease Models, Animal ; Female ; Hypoxia ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Vascular Endothelial Growth Factor ; analysis ; Retina ; chemistry ; pathology ; Retinal Diseases ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; analysis

OBJECTIVETo investigate the associations of guanylate cyclase C (GC-C) mRNA and cytokeratin 20 (CK20) mRNA with metastasis and prognosis in early to moderate colorectal cancer patients.

METHODSGC-C mRNA and CK 20 mRNA in peripheral blood of 74 colorectal cancer patients without distant metastasis were detected by fluorescent quantitative PCR (FQ-PCR). Based on their clinicopathological and postoperative follow-up data, the relationship and clinical significance of these data with metastasis hazards and prognosis factors were analyzed.

RESULTSThe positive rate of GC-C mRNA in 74 colorectal cancer patients was 33.8% (25/74), and CK20 mRNA was 31.1% (23/74). The 1-, 2-, 3- year disease-free survival rates of patients were 94.6%, 82.4% and 78.4% respectively. There were significant differences in positive rates of GC-C mRNA and CK20 mRNA, tumor differentiation, mesentery lymph node metastasis, tumor embolus in vessel and postoperative chemotherapy associated with 3-year disease free survival rate by Kaplan-Meier analysis (all P<0.05). While mesentery lymph node metastasis and tumor embolus in vessel were independent risk factors of 3-year disease-free survival (P<0.05). CK20 mRNA and tumor embolus in vessel were independent risk factors of 3-year disease-free survival by analysis stratified with clinical stage (P<0.05).

CONCLUSIONSDetection of CK20 mRNA and GC-C mRNA in peripheral blood may be important for early detection of early metastasis of colorectal cancer.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; blood ; Female ; Follow-Up Studies ; Humans ; Keratin-20 ; blood ; genetics ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; blood ; genetics ; Receptors, Atrial Natriuretic Factor ; blood ; genetics ; Risk Factors

OBJECTIVETo discuss the mechanism of rectal cancer apoptosis induced by preoperative chemoradiotherapy and evaluate its effect by detection of apoptosis related proteins in locally advanced colorectal cancer patients who had received preoperative chemoradiation.

METHODSTo detect Bcl-XL and Bax expression in rectal cancer before and after chemoradiotherapy by EnVision method, combined with patients clinical and pathological index, statistically analysis and evaluation their relationship and clinical significance.

RESULTSPatients with or without tumor shrinkage after preoperative chemoradiotherapy was 13 cases and 21 cases. While the positive rate of Bcl-XL in rectal cancer before and after chemoradiotherapy were 58.8% (20/34) and 52.9% (18/34), respectively. There were significant difference between Bcl-XL change before and after chemoradiation with tumor size, tumor cells shrinkage and operation pattern. The positive rate of Bax in rectal cancer before and after chemoradiotherapy were 32.4% (11/34) and 44.1% (15/34), respectively. There were no significant difference between Bax change before and after chemoradiotherapy with tumor cells shrinkage. There were statistically significant difference between Bax ratio (χ(2) = 9.607, P = 0.048) before and after chemoradiation while there were no significant difference between Bcl-XL/Bax ratio before and after chemoradiation with tumor shrinkage. According to layered analysis with preoperative therapy, there were statistically significant difference (χ(2) = 13.964, P = 0.007) between Bcl-XL change with operation pattern while the same of significant difference between Bax change with tumor infiltration and tumor shrinkage (χ(2) = 10.806 and 10.455, both P < 0.05).

CONCLUSIONSPreoperative chemoradiation can influence rectal cancer cell's apoptosis and treatment effect by changing Bcl-XL and Bax expression. Bcl-XL downregulation and Bax upregulation have shown important function in colorectal cancer cell apoptosis which induced by preoperative chemoradiation, it can also improve the effection of chemoradiation in rectal cancer.

Adult ; Aged ; Apoptosis ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms ; metabolism ; therapy ; Tumor Suppressor Protein p53 ; metabolism ; bcl-2-Associated X Protein ; metabolism ; bcl-X Protein ; metabolism

OBJECTIVETo study the effects of benzo(a)pyrene (BaP) on the cell cycle distribution and activities of mitogen-activated protein kinase (MAPK) signal molecules (ERK1/2, JNK1/2 and p38) in human embryo lung cells (HELF), and to investigate the relationship between alterations of MAPK protein phosphorylation and the cell cycle distributions.

METHODSThe phosphorylation of MAPK were induced by exposing HELF cells to BaP at 0.1, 0.5, 2.5 and 12.5 micromol/L. The phosphorylation and protein expression levels of ERK1/2, JNK1/2 and p38 were determined through western-blotting assay. And the flow cytometry assay was used to measure the cell cycle effects in HELF cells after treatment with 2.5 micromol/L BaP for 24 h.

RESULTSThe phosphorylation levels of ERK1/2, JNK1/2 and p38 were significantly increased through BaP exposure. In addition, the phosphorylation of these three MAPKs has similar alteration pattern. We found that exposure of cells to 2.5 microM of BaP for 24 h resulted in a decrease of G(0) and G(1) population by 11.9% (F = 41.38, P < 0.01) and an increase of S population by 17.2% (F = 68.13, P < 0.01). Three chemical inhibitors of MAPK (AG126, SP600125 and SB203580) could significantly inhibit the cell cycle alteration because of BaP treatment.

CONCLUSIONERK1/2, JNK1/2 and p38 could positively regulate the BaP independently induced cell cycle alterations.

Benzo(a)pyrene ; toxicity ; Cell Cycle ; drug effects ; Cells, Cultured ; Fibroblasts ; drug effects ; metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Lung ; cytology ; embryology ; MAP Kinase Kinase 4 ; metabolism ; MAP Kinase Signaling System ; drug effects ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinase 8 ; metabolism ; Mitogen-Activated Protein Kinase 9 ; metabolism ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo evaluate the efficacy of preoperative radiochemotherapy and investigate the influencing factors in rectal cancer.

METHODSFifty-three patients with locally advanced rectal cancer were treated with radiochemotherapy before surgery. Three-field technique of radiation therapy was administered with 46 Gy, 2 Gy per fraction, five times a week. Two cycles of chemotherapy were carried out at day 1, 2 and day 21, 22 during the radiation course. Surgery was performed 4-6 weeks after the radiochemotherapy. Response of preoperative radiochemotherapy was evaluated in all the patients by endoscopic ultrasonography (EUS), spiral computed tomography (SCT) and pathology. Influencing factors of the efficacy of radiochemotherapy were evaluated by univariate and Logistic analysis.

RESULTSUnivariate analysis revealed that tumor size and histological grading were associated with the efficacy of preoperative radiochemotherapy. Logistic regression analysis showed that only tumor size was the significant predictive factor for response to preoperative radiochemotherapy. All patients underwent surgical resection after preoperative radiochemotherapy. The tumor was reduced by an average of 32.1%. T-level down-staging was 64.2%. Nodal negativity was 58.1%. Complete pathologic remission occurred in 11 patients.

CONCLUSIONSPreoperative radiochemotherapy can shrink the primary tumor and decrease lymph node metastasis rate. Patient with small tumor may have better response to preoperative radiochemotherapy.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; drug therapy ; radiotherapy ; therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the effect of a 10-day course of triptolide (TP) on rat cytochrome (CY) P3A4 activity, and on the pharmacokinetics of cyclophosphamide (CPA).

METHODSIn the pharmacokinetics experiment, rats were orally given 0.9% NaCl solution (n=5) and TP [1.2 (mg/kg·d)] for 10 days and a single dose of CPA was administered intravenously (100 mg/kg) to rats on day 11. Blood samples were collected up to 4 h at predetermined time intervals, the plasma concentration of CPA was determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were determined. In the in vitro CYP3A4 activity inhibition research, rat blank liver microsomes were divided into 3 groups: a control group, a TS (5 μL, 200 μmol/L) with TP (5 μL, 12.5 μmol/L) group, a TS with ketoconazole (5 μL, 1 μmol/L) group. Concentration of 6β-hydroxylated testosterone (6β-OHT) in liver microsomes was measured by HPLC and the activity of CYP 3A4 was calculated through the following formula: Einhibitor/Econtrol × 100%=Cinhibitor/Ccontrol × 100%.

RESULTSCompared with the control group, the area under the plasma concentration-time curve (AUC0-∞) of CPA was significantly increased by 229.05% pretreated with TP (P<0.01). Peak plasma concentrations (Cmax) of CPA was significantly increased and plasma half-life was correspondingly extended. The CYP3A4 activity was significantly inhibited by ketoconazole 93.5%±0.2% and TP 84.6%±0.3% compared with the control group (P<0.01 and P<0.05, respectively).

CONCLUSIONOur results strongly suggested that long-term oral intake of TP can distinctly inhibit the CYP3A4 activity and this inhibition evidently decrease the formation of toxic metabolites of CPA.

Animals ; Cyclophosphamide ; pharmacokinetics ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; pharmacology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Herb-Drug Interactions ; Hydroxytestosterones ; metabolism ; Immunosuppressive Agents ; pharmacokinetics ; Injections, Intravenous ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; metabolism ; Phenanthrenes ; pharmacology ; Rats, Sprague-Dawley