ABSTRACT
In recent years, two novel proteins in the ribosomes of mycobacteria have been discovered by cryo-electron microscopy. The protein bS22 is located near the decoding center of the 30S subunit, and the protein bL37 is located near the peptidyl transferase center of the 50S subunit. Since these two proteins bind to conserved regions of the ribosome targeted by antibiotics, it is speculated that they might affect the binding of related drugs to these targets. Therefore, we knocked out the genes encoding these two proteins in wild-type Mycolicibacterium smegmatis mc2155 through homologous recombination, and then determined the growth curves of these mutants and their sensitivity to related antibiotics. The results showed that compared with the wild-type strain, the growth rate of these two mutants did not change significantly. However, mutant ΔbS22 showed increased sensitivity to capreomycin, kanamycin, amikacin, streptomycin, gentamicin, paromomycin, and hygromycin B, while mutant ΔbL37 showed increased sensitivity to linezolid. These changes in antibiotics sensitivity were restored by gene complementation. This study hints at the possibility of using ribosomal proteins bS22 and bL37 as targets for drug design.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cryoelectron Microscopy , Mycobacterium/genetics , Ribosomal Proteins/genetics , Ribosomes/metabolismABSTRACT
Objective To observe the sensitization of lidocaine on subcutaneous hepatoma H22-bearing mice and abdominal cavity H22 tumor-bearing mice treated by mitomycin. Methods According to the random number table method, the mice were divided into subcutaneous tumor-bearing group and abdominal cavity tumor-bearing group, with 15 mice in each group. The mice in the two groups were further divided into three subgroups: model group, mitomycin group, mitomycin+lidocaine group, with 5 mice in each subgroup. The day before the intraperitoneal injection, the density of H22 cells obtained from peritoneal culture of one mouse was adjusted to 5 ×106/ml. Subcutaneous tumor-bearing group mice were injected H22 cells into the right armpit, and abdominal cavity tumor-bearing group mice were injected H22 cells into the abdominal cavity, 0.2 ml per mouse. Intraperitoneal injection was given after inoculation for 24 h (the experiment day 1), followed by intraperitoneal injection on day 5 and 9. Univariate ANOVA analysis and t test were used to analyze the solid tumor weight and tumor inhibition rate on the 11th day of subcutaneous tumor-bearing mice, and the survival time and life extension rate within 60 days of abdominal cavity tumor-bearing mice. Results The solid tumor weight of subcutaneous tumor-bearing mice model group, mitomycin group and mitomycin + lidocaine group were (3.77 ±1.02) g, (1.67 ±0.28) g, (0.74 ±0.19) g, respectively, and the differences in the three groups were statistically different (F = 31.753, P < 0.01); compared with the subcutaneous model group, the subcutaneous solid tumor weights of mitomycin group and mitomycin +lidocaine group were decreased and the differences were both statistically different (t=2.10, P<0.01; t=3.04, P<0.01); the subcutaneous solid tumor weight of mitomycin+lidocaine group was lower than that of mitomycin group (t= 0.93, P= 0.034). The tumor inhibition rate of mitomycin group and mitomycin +lidocaine group reached 55.70％ and 80.37％ respectively. The survival time of abdominal cavity tumor-bearing mice in model group, mitomycin group and mitomycin + lidocaine group was (16.80±0.84) d, (28.80± 6.30) d, (40.40±12.86) d, respectively, and the differences in the three groups were statistically different (F=10.155, P=0.003); compared with the abdominal cavity tumor-bearing mice model group, the survival time of mice in mitomycin group and mitomycin + lidocaine group was prolonged (t= 12.00, P= 0.041; t= 23.60, P= 0.001), and it was found that survival time in mitomycin + lidocaine group was longer than that in mitomycin group (t=11.60, P=0.047). The life extension rate of mitomycin group and mitomycin+lidocaine group reached 71.43％ and 140.48％ respectively. Conclusion Lidocaine can increase the sensitization of mitomycin on hepatoma H22-bearing mice.
ABSTRACT
Objective To investigate the clinical applications of nuclear matrix protein 22 (NMP22) and urine cytology in early diagnosis,monitoringrecurrence and determining prognosis of bladder cancer.Methods Ninty-six urine specimens,including 45 cases before the resection of bladder cancer (pathologically confirmed),20 cases after the resection of bladder cancer and 31 cases with benign urinary tract condition,were both selected in detecting NMP22 by enzyme-linked i mmunosorbent assay (ELISA),and the results were compared with urinary cytology by x2 test.Results The NMP22 content of 45 cases before the resection of bladder cancer was 9.3 to 112.5 U/mL,the median was 48.7 U/mL.The NMP22 content of 31 cases with benign urinary tract condition was from 2.1 to 14.7 U/mL,the median was 7.9 U/mL.The NMP22 content of 20 cases after the resection of bladder cancer was from 4.3 to 18.7 U/mL,the median was 8.9 U/mL.The median of NMP22 before the resection of bladder cancer was significantly higher than the median in patients with benign urinary,the difference was statistically significant (P ＜0.05).Considering NMP22 ≥ 10 U/mL as the critical value,the sensitivity of the NMP22 in diagnosing bladder cancer was 82.2％ and the specificity was 70.9％.And the sensitivity of urine cytology was 31.1％ and the specificity was 100％.The recurrence of 9 cases was confirmed by cystoscopy in 20 cases after the resection of bladder cancer.Conclusion The NMP22 can be a effective biomarker in the early screeningand postoperative follow-up of bladder cancer.