Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) plays the pivotal role in tumor development and metastasis, so it is a promising drug target in malignancy. To acquire MT1-MMP specific binding peptides, we first analyzed MMPs sequences to find the divergent and specific sequence of MT1-MMP by bioinformatics approach, then set the specific sequence as the sense peptide target and designed antisense peptide library. Finally, by means of molecular docking, molecular dynamics simulation and in vitro cell assays, we screened the antisense peptide library against MT1-MMP and further studied the obtained specific peptides. Here, we identified the divergent and specific sequence of AYIREGHE (Named MT1-loop) located in MT1-MMP loop by multiple sequence alignment and established the antisense peptides library with capacity of 1 536 sequences. After two rounds of virtual screening, we obtained five antisense peptides with Rerankscores in the top for further screening. They all interacted with MT1-MMP, and docked well at the active site composed of MT1-loop sequence. Analysis of the affinities of these five antisense peptides to other MMPs (MMP1-3, MMP7-13, MMP14 HPX, MMP16) revealed that the peptide FVTFPYIR was more specific to MT1-MMP. Molecular dynamics simulation showed that the peptide FVTFPYIR might affect the stability of MT1-MMP and thus have effects on its activities. Meanwhile, the peptide FVTFPYIR could specifically inhibit the growth of MG63 and MDA-MB-231 tumor cells both of which expressed MT1-MMP. The work provides a new insight and way for the development of antitumor lead peptides targeting MT1-MMP.
Amino Acid Sequence ; Humans ; Matrix Metalloproteinase 14 ; chemistry ; Molecular Dynamics Simulation ; Neoplasms ; Peptide Library ; Peptides ; chemistry

Objective To evaluate the role of interleukin-12 (IL-12) in the spinal cord in the maintenance of arthritic pain (AP) in rats.Methods Adult male Sprague-Dawley rats, aged 6-8 weeks,weighing 200-300 g, were randomly divided into 4 groups using a random number table: control group (group C, n=6);AP group (n=9);phosphate buffer solution (PBS) group (n=6);IL-12 antibody group (n =6).AP was induced by injecting 50 μl of complete Freund' s adjuvant into the ankle joint cavity of the left hindpaw of rats anesthetized with isoflurane.Goat anti-rat IL-12 antibody 1.50 μg (20 μl) was intrathecally injected on 9 days after establishment of the model in group IL-12 antibody, while 0.01 mol/L PBS (20 μl) was administered in group PBS.The mechanical paw withdrawal threshold to yon Frey filament stimulation (MWT) was measured before establishment of the model (baseline) and on 9 and 10 days after establishment of the model.The rats were sacrificed after the last measurement of pain threshold, and the L4 6 segments of the spinal cord were obtained for detection of IL-12 expression in the spinal dorsal horn (by immunofluorescence) , and the co-expression of IL-12 and glial fibrillary acidic protein (an astrocyte marker) was examined simultaneously in group AP.Results Compared with group C, the MWT was significantly decreased, and the expression of IL-12 was up-regulated on 9 and 10 days after establishment of the model in AP, PBS and IL-12 antibody groups.Compared with group AP, the MWT was significantly increased at 10 days after establishment of the model, and the expression of IL-12 was down-regulated in group IL-12 antibody, and no significant change was found in the MWT at 10 days after establishment of the model and expression of IL-12 in group PBS.IL-12 was co-expressed with glial fibrillary acidic protein in group AP.Conclusion IL-12 in the spinal cord is involved in the maintenance of AP in rats.

Objective: To study the epidemiology and the etiology characteristics of first imported severe fever with thrombocytopenia syndrome (SFTS) case reported in Shenzhen city in 2017. Methods: Data on descriptive epidemiology was collected to study the characteristics to the epidemic. The serum sample collected from the suspect SFTS case was detected for IgM, IgG by ELISA and severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) nucleic acid by real-time RT-PCR. The samples were further inoculated in Vero cell for virus isolation. The partial fragements of L and S gene were amplified by RT-PCR and sequenced to construct homology comparison and phylogenetic tree with the strains isolated from other areas. Results: The case was laboratory confirmed imported SFTS case in Shenzhen on May 2017. IgM antibody and RNA of SFTSV were detected in the serum sample. SFTSV named GDSZ01/2017/China was successfully isolated from the serum sample. The high nucleotide homology of L and S genome segments were found at 95.3%-98.2% and 93.8%-98.8% with other representative strains from the popular provinces, respectively. The phylogenetic tree indicated that GDSZ01 was most close to SDTA_3 strain, next to strains in Hubei procince. The isolated SFTSV belonged to genotype C3 with HB29, HB154. Conclusions The virological, serological and molecular features showed that the imported case of SFTS in 2017 was caused by SFTSV C3 genotype.

Objective:To investigate the epidemiological characteristics of dengue fever and genotyping of the epidemic strains of dengue virus in Shenzhen City in 2018.Methods:Descriptive epidemiological analysis was used to analyze dengue fever prevalence in Shenzhen City in 2018. Blood samples of patients with dengue fever were collected. The colloidal gold immunochromatography was used to detect serum specific IgM and IgG antibodies, and real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect viral nucleic acids and to identify genotypes. The E gene sequence of isolated virus strain was amplified by reverse transcription PCR. Homology comparison and phylogenetic tree of dengue fever epidemic strains in different countries and regions were conducted. Results:A total of 234 cases of dengue fever were reported in Shenzhen City from January 1 to December 31, 2018. The incidence rate was 1.87/100 000. There were 144 (61.54%) local patients and 90 (38.46%) imported patients, who were mainly from Southeast Asia and surrounding cities. Two hundred and two (86.32%) cases were reported during the epidemic peak period from August to November of the year. The patients mainly aged 20 to 50 years old (195 cases, 83.33%). Dengue virus type (DENV)-1 accounted for 86.01%(166/193), DENV-2 accounted for 10.36%(20/193), DENV-3 accounted for 2.59%(5/193), and DENV-4 accounted for 1.04%(2/193). The local cases were all infected with DENV-1. The homologies of nucleotide sequence and the deduced amino acid sequence of E gene of 24 DENV-1 strains with HAWAII45 strain were 93.0% to 94.6% and 96.6% to 97.2%, respectively. The phylogenetic tree of DENV-1 strains revealed that 23 strains belonged to genotypeⅠ, and one strain belonged to genotype Ⅳ which was the first reported imported cases in Shenzhen City. The homologies of nucleotide sequence and the deduced amino acid sequence of E gene of six DENV-2 strains with NGC strain were 93.1%to 93.9% and 97.0% to 97.8%, respectively. The phylogenetic tree of DENV-2 strains showed that two strains belonged to genotype Cosmopolitan and four strains belonged to genotype Asian Ⅰ, which were first reported in Shenzhen City. Conclusions:The epidemic of dengue fever in Shenzhen City in 2018 has the characteristics of coexistence of local and imported transmission. The main epidemic genotype is DENV-1. It infers that the major virus strains may be imported from Southeast Asia countries and surrounding cities. Therefore, attention should be paid to the epidemic trend of local dengue fever.

Objective:To investigate the clinical outcome after surgery and first 131I treatment in patients with moderate-risk papillary thyroid cancer (PTC), and analyze the relevant factors that affect the therapeutic effect. Methods:From January 2018 to April 2019, 135 patients (48 males, 87 females; age (42.7±11.1) years) with moderate-risk PTC in the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into excellent response (ER) group, inderteriminate response (IDR) group, biochemical incomplete response (BIR) group and structural incomplete response (SIR) group, of which IDR, BIR, SIR were collectively referred to as the non-ER group. χ2 test and Mann-Whitney U test were used to compare the general clinical features between the ER and non-ER groups, and then multivariate logistic regression analysis was performed. The predicted value of pre-ablation stimulated thyroglobulin (ps-Tg) to ER was assessed by ROC curve analysis. Results:The treatment responses of 94 patients were ER, and those of 41 were non-ER. The differences in tumor size (0.80(0.50, 1.10) vs 1.00(0.55, 1.50) cm; U=1 491.50, P=0.036), the number of metastatic lymph nodes (3(2, 5) vs 4(2, 12); U=1 422.00, P=0.015), metastatic lymph node size (0.50(0.30, 0.65) vs 0.50(0.30, 1.45) cm; U=1 396.50, P=0.013), metastatic lymph node involvement rate (50%(30%, 70%) vs 60%(50%, 85%); U=1 441.50, P=0.024), metastatic lymph node location (central/lateral: 76/18 vs 24/17; χ2=7.40, P=0.007) and ps-Tg level (2.1(0.8, 5.3) vs 14.0(3.2, 35.2) μg/L; U=680.00, P<0.001) were statistically significant between the ER and non-ER groups. Multivariate logistic regression analysis showed that ps-Tg (odds ratio ( OR)=1.200, 95% CI: 1.107-1.302, P<0.001) was an independent factor influencing ER. The cut-off value of ps-Tg for predicting ER was 7.38 μg/L, with the sensitivity and specificity of 68.3%(28/41) and 87.2%(82/94) respectively. Conclusion:Moderate-risk PTC patients with smaller tumor size, fewer metastatic lymph nodes, lower metastatic lymph node involvement rate, metastatic lymph nodes in central area, smaller metastatic lymph node size, and ps-Tg<7.38 μg/L have better therapeutic effect after initial 131I treatment.