Research progress on efflux pump inhibitors of Mycobacterium tuberculosis in recent years / 药学学报

Currently, the resistance of first-line anti-tuberculosis drugs has made the prevention and treatment of tuberculosis increasingly difficult, posing a serious threat to global public health. Several studies have shown that efflux pumps are one of the important causes for bacteria to develop multi-drug resistance and extremely-drug resistance, and efflux pump inhibitors can inhibit the efflux of antibacterial drugs, thereby reducing bacterial drug resistance. Numerous natural products and synthetic compounds have been reported to possess efflux pump inhibitory activity, but they have not been applied in clinical settings because of their toxicity, pharmacokinetic properties, etc. Therefore, we summarized the efflux pump inhibitory activity, antimicrobial activity, and structure-activity relationships of reported efflux pump inhibitors against Mycobacterium tuberculosis in recent years, providing references for the development of new efflux pump inhibitors with better activity and lower toxicity.

Immunochromatographic Assay for Maximal Residual Limit-based Multiple Quantitative Determination of Triazophos in Agro Products / 分析化学

A novel immunochromatographic assay was developed, which could provide visual evidence of triazophos in agro products, and also could directly identify the safety status by setting visual cut-off limit of detection in maximal residual limit ( MRL) value. Three test lines ( T1, T2, T3) were applied to the nitrocellulose membrane with different concentrations of Triazophos-OVA, and one control line (C) was settled with goat anti mouse IgG antibody. Thereafter, by combining with conjugate pad which immobilized monoclonal antibody labeled with 20 nm Colloidal gold particles, absorbent pad and PVC plate, a chromatographic test strip was assembled. With optimization of sample extraction and solvents selection, the test strips were employed for the determination of triazophos in rice, cabbage and apple. The results revealed that the cut-off limit of detection could reach 0. 005, 0. 01 and 0. 02 μg / mL represented by test line T3, T2 and T1, respectively. After modification, the cut-off limit of detection was resettled to 0. 05, 0. 1 and 0. 2 μg / mL according to the MRL values which enforced by the national standard of GB2763. Using acetonitrile for the sample extraction, the extracts were diluted 10 times or solvent exchanged with equivalent volume by PBS solution, and then tested by strips descripted above mentioned. The two test strips could precisely identified the safety status of agro product with MRL as threshold within 8-12 min. Furthermore, the residues value of triazophos could be quantified by the multiple quantitative test lines. Parallel GC data indicated that the strip had no false negative. This MRL-based multiple quantitative triazophos detection strip would provide a simple, direct, accurate and the most intuitionistic performance for the evaluation of agro product safety.

Immunochromatographic Assay for Detection of Imidaclothiz Based on Upconversion Fluorescence Labeling / 分析化学

A simple,rapid and sensitive upconversion immunochromatographic assay(UICA) was developed to detect imidaclothiz using NaYF4:Yb,Er upconversion nanoparticles(UCNPs) labeled with anti-imidaclothiz monoclonal antibody. The amino-modified UCNPs were conjugated with anti-imidaclothiz monoclonal antibody to prepare the UICA strip,which could realize the quantitative detection of imidaclothiz using a fluorescence photometer with an external 980 nm laser source. The working conditions of the UICA were systematically optimized, and the sensitivity, specificity, precision and accuracy were assessed by the studies of cross-reactivity (CR), spiked recovery and validation with HPLC. Under the optimal conditions (pH 8. 0, 0.3 mol/L NaCl,2.5% methanol and 0.2% PEG2000), the UICA could be completed in 25 min for the detection of imidaclothiz. The half-maximal inhibition concentration (IC50), limit of detection (IC10) and linear range (IC10-IC90) were 97.37 ng/mL,26.30 ng/mL and 26.30-363.08 ng/mL, respectively. The UICA had no CR with the analogues of imidaclothiz except for imidacloprid. The average spiked recoveries were 71.8%-97.2% with the relative standard deviations of 0.7%-10.7% in the matrices of paddy water, soil,pear,peach,wheat,cucumber,tomato and rice. The detection results of UICA for the authentic paddy water and pear samples were consistent with that of high performance liquid chromatography (HPLC).

Expression of soluble vascular endothelial growth factor receptor-1 and placental growth factor in fetal growth restriction cases and intervention effect of tetramethylpyrazine

OBJECTIVE@#To investigate the expression of soluble vascular endothelial growth factor receptor-1 (sFlt-1) and placental growth factor (PLGF) in the fetal growth restriction (FGR) cases and the intervention mechanism of tetramethylpyrazine.@*METHODS@#A total of 60 fetal growth restriction cases that admitted to our hospital were randomly divided into ligustrazine intervention group (group A) and nutritional support group (group B). A total of 50 healthy pregnant women were also enrolled as control group (group C). Expression level of maternal serum sFlt1, PLGF and fetal growth parameters including HC, AC, FL, BPD, EFW as well as placenta PLGF, sFlt-1 mRNA expression were recorded and compared among the three groups. A total of 15 SD rats were selected and were divided into three groups, TMP group, alcohol and tobacco group and blank control group. Three groups of rats were dissected on the twentieth day of gestation.@*RESULTS@#Expression level of sFlt-1 and PLGF in group A was not significantly different from that of group C (P>0.05); but significant difference in SFlt1 and PLGF expression level was observed between group C and group B (P0.05). There was significant difference in PLGF between FGR group with treatment and FGR group without treatment or control group (P<0.01).@*CONCLUSIONS@#PLGF level is decreased and sFlt-1 increased in patients suffered from fetal growth restriction, and FGR rats show increased sFlt-1 and decreased PLGF, thus they can be indicator of the fetal growth restriction. Ligustrazine can effectively improve sFlt-1, PLGF expression level in fetal growth restriction cases, which can be used as treatment for FGR.

The association of hippocampal glutamate with depression and the effects on gastric mobility / 中国应用生理学杂志

<p><b>AIM</b>To explore the relationship between the pathology of depression and glutamate (Glu) in hippocampus, and the effect on gastric mobility.</p><p><b>METHODS</b>Depression model was established by using the chronic unpredicted mild stress (CUMS). And stereotaxic and intra-hippocampal microinjection were also used in this experiment. Rat emotion and behaviors were observed by the change in body weight, sucrose preference-test, open field-test and forced swimming-test. Intragastric pressure and mobility were recorded with the instrument of Powerlab/8sp.</p><p><b>RESULTS</b>Compared with the control, 21-day CUMS significantly reduced the increase in body weight, rat sucrose preference, locomotor activity and rearing in open field test, while it significantly increased duration of immobility time in forced swimming test. Meanwhile, magnitudes of intragastric pressure and mobility were significantly declined after 21 days CUMS. Microinjection of Glu into hippocampus mimics the behaviors which were produced in CUMS. The down-rang of gastric mobility in the group of Glu injection was smaller than CUMS, but was much larger than the control. Intrahippocampal microinjection of MK-801 attenuated depression-like behaviors induced by stress, weakened stress-induced inhibition of intragastric pressure, and augmented the magnitudes of gastric contraction.</p><p><b>CONCLUSION</b>Glu and NMDA receptor in hippocampus are to do much with the etiology of stress- induced depression. They are not only concerned with behavioral changes induced by stress, but also with the variation of gastric activities, nevertheless, differences exist between the effects of behaviors and gastric activities.</p>

Artesunate suppresses human endometrial carcinoma RL95-2 cell proliferation by inducing cell apoptosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of artesunate on human endometrial carcinoma RL95-2 cell line proliferation in vitro and the possible mechanisms.</p><p><b>METHODS</b>The inhibitory effect of artesunate on the cell proliferation was assessed with MTT assay. Transmission electron miscrosopy was used to observe the morphological change of the cells after the treatment. Flow cytometry was performed to examine the changes in the cell cycle, reactive oxygen species (ROS) levels (with DCFH-DA labeling) and mitochondrial membrane potential (rhodamine123 staining), and caspase-3 activity was detected by immunohistochemistry.</p><p><b>RESULTS</b>Artesunate inhibited the proliferation of RL95-2 cells with an IC(50) of 26.29 microg/ml. Transmission electron microscopy revealed early apoptotic changes of the cells with obvious chromatin fragmentation. The cell cycle arrest at G(0)/G(1) phase was observed by flow cytometry, and immunohistochemistry demonstrated caspase-3 positivity in cytoplasm. ROS generation in the cells increased obviously after treatment with artesunate for 72 h, which also resulted in lowered mitochondrial membrane potential.</p><p><b>CONCLUSION</b>Artesunate suppressed the proliferation of RL95-2 cells in vitro possibly by inducing cell apoptosis.</p>

Expression of peroxisome proliferator-activated receptor gamma in glioma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression and significance of peroxisome proliferators-activated receptor gamma (PPAR gamma) in human glioma.</p><p><b>METHODS</b>Immunohistochemical staining for PPAR gamma was performed using biopsy specimens of human glioma of various histological types. Expression of PPAR gamma and GFAP in glioma cell lines SWO-38, U251 and SHG-44 were analyzed using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Immunohistochemical study showed that PPAR gamma was expressed in glioma tissues with positive rate of 37.5%. Western blotting and RT-PCR showed that PPAR gamma was expressed in both glioma cell lines SWO-38 and U251, but not in SHG-44 cells. However, high expression of GFAP was detected in SHG-44 cells.</p><p><b>CONCLUSION</b>PPAR gamma is associated with carcinogens of glioma. Actived PPAR gamma by agonist may be a novel approach to the treatment of glioma.</p>

Effects of exogenous human chorionic gonadotropin on nude mice bearing endometrial carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of exogenous human chorionic gonadotropin (hCG) on nude mice bearing transplanted endometrial carcinoma.</p><p><b>METHODS</b>Human endometrial carcinoma xenograft was transplanted in nude mice, and the effects of hCG injection on the tumor growth was evaluated according to tumorigenesis and xenograft weights. The expression of Ki-67 in the tumor was determined by immunohistochemistry, and HE staining was performed for morphological observation and measurement of the necrosis area in the tumor. The effect of hCG on fibrosis in the tumor was evaluated with Masson staining.</p><p><b>RESULTS</b>Compared to normal saline-treated tumor-bearing mice, the mice with hCG treatment showed increased tumor weight. HE staining for tumors in HCG-treatment group visualized tumor cell arrangement in glandular structure with smaller necrosis area, and Masson staining identified thick and compact collagen fibers as compared with the thin and loosely arranged fibers in saline-treated group. No significant difference was found in the Ki-67 expression in the tumors between the two groups.</p><p><b>CONCLUSION</b>Exogenous hCG can promote the differentiation of the endometrial carcinoma cells in vivo.</p>

Differentially expressed genes between a fertile patient and an infertile patient in a large Chinese androgen insensitivity syndrome pedigree / 中国医学科学院学报

<p><b>OBJECTIVE</b>To screen and identify differentially expressed genes between a fertile patient and another infertile patient who belonged to a large Chinese pedigree affected with androgen insensitivity syndrome (AIS).</p><p><b>METHODS</b>We constructed the forward and reversed subtracted libraries using genital skin fibroblasts (GSF), which were obtained from the fertile patient MJ and infertile patient ZGJ, as tester respectively. Candidate clones were screened with colony in situ hybridization, dot blot, and Southern blot analysis step by step and conformed with Northern blot analysis. The potential positive clones were sequenced and the homology of the sequences was analyzed.</p><p><b>RESULTS</b>The forward and reversed subtracted libraries containing differentially expressed pattern of two GSF cell lines were constructed. Two positive clones identified by Northern blot were obtained in the reversed subtracted library. Eleven candidate clones from the two libraries that failed to hybridize with both RNA populations were obtained simultaneously, which might represent differentially expressed low abundance transcripts. Sequencing results and homology analysis demonstrated that the two positive clones were significantly homologous with the genes of autotaxin-t and calcium binding protein calcyclin (S100A6), respectively.</p><p><b>CONCLUSIONS</b>Two positive clones and eleven clones showing no hybridization signals may represent differentially expressed genes between the two GSFs. This finding may be useful to elucidate the molecular mechanisms leading to phenotypic variation and preserved fertility of the AIS pedigree.</p>