AIM:To investigate the effects of bcl-3 gene on the migration and apoptosis of human colon cancer cell line RKO, and the changes of cyclin D1 and apoptosis-related proteins.METHODS:After silencing of bcl-3 gene expression in human colon cancer cell line RKO by lentiviral vector with RNA interference, the changes of RKO cell migration ability were investigated by wound healing assay.The changes of RKO cell apoptotic rate after bcl-3 gene silencing were detected by flow cytometry with Annexin V/PI staining.The protein expression of cyclin D1 and apoptosis-related proteins in the RKO cells after bcl-3 gene silencing was determined by Western blot.RESULTS:The wound healing rates of the RKO cells were 84.00% and 40.00% before and after bcl-3 gene silencing, respectively, with statistically significant difference (P<0.05).Annexin V/PI staining showed that the cell apoptotic rates were 12.89% and 59.67% before and after bcl-3 gene silencing, respectively, when RKO cells were treated with 5 μmol/L cisplatin for 24 h, with statistically significant difference (P<0.05).The expression of cyclin D1 decreased, while the expression of Bax increased after bcl-3 gene silencing (P<0.05).CONCLUSION:After bcl-3 gene silencing, the migration ability of RKO cells decreases, and the apoptotic rate increases, accompanying with the changes of cyclin D1 and Bax.bcl-3 gene can affect the apoptosis of RKO cells by changing the expression of cyclin D1 and Bax.

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.

Communion is an important way to study.Interaction is the most notable character of network.This paper introduces some experience on how to bring net interaction into play in the network-based medical teaching.

Objective To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with gabapentin for treatment of recurrent pain after trigeminal radiofrequency thermocoagulation.Methods Forty patients of both sexes suffering from recurrent pain after trigeminal radiofrequency thermocoagulation,who refused surgical treatment,aged 45-80 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,with visual analog scale score ≥4,with the course of recurrent pain 0.5-17.0 months,were randomized into 2 groups (n =20 each) using a random number table:gabapentin group (group A) and gabapentin plus rTMS group (group B).The patients were treated with 2 courses of rTMS in total (5 days for 1 course,1 time per day) and with the second course at a 2-day interval in group B.Effective analgesia and pain relief were recorded within 6 months after treatment,and the therapeutic efficacy was evaluated according to the modified Macnab criteria.The daily consumption of gabapentin and development of rTMS-and gabapentin-related adverse reactions were recorded.Results No rTMS-related adverse reactions were found in group B.Compared with group A,the rates of effective analgesia and pain relief were significantly increased,the therapeutic efficacy was enhanced,the daily consumption of gabapentin was decreased,and the incidence of gabapentin-related adverse reactions was decreased in group B (P＜0.05).Conclusion Combination of rTMS and gabapentin produces better efficacy than gabapentin alone when used to treat the recurrent pain after trigeminal radiofrequency thermocoagulation,and the safety is good.

To search for fluoroquinolones(FQs)with antitumor activity;the C-3 carboxylic acid group of peflox-acin (1)was replaced by fused heterocyclic core;and twelve novel thiazolo[3;2-b][1;2;4]triazole heterocycles(6a-6l)were designed and synthesized.The structures of target compounds were characterized by elemental anal-ysis and spectral data.The results of the in vitro antiproliferative effect on SMMC-7721;L1210 and HL60 cell lines showed that the title compounds exhibited more significant antitumor activity than both of the pefloxacin and the corresponding opening-ring intermediates(5 a-5 l).Among them;the target compounds which possess a ben-zene ring bearing a hydroxyl group (6e)or a fluorine atom (6j)exhibited more potent antiproliferative effect on SMMC-7721 cells than other compounds.Therefore;the antitumor fluoroquinolones can be designed by replacing the C-3 carboxylic acid group of fluoroquinolones with the thiazolo[3;2-b][1;2;4]triazole moiety.

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, β-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, β-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.

To improve the antitumor activity of fluoroquinolones for a promising development of druggability, twelve novel fluoroquinolone C-3 s-triazole sulfide-one thiosemicarbazone derivatives(6a-6l)were designed and synthesized with a functionalized sulfide-one thiosemicarbazone as a modified side-chain for the C-3 bioisteric s-triazole ring of pefloxacin(1). The structures were characterized by elemental analysis and spectral data。The in vitro antitumor activity of novel compounds against SMMC-7721, L1210 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds exhibited more significantly antiproliferative activity than either the parent 1 or the corresponding sulfide-one intermediates(5a-5l). In particular, compounds bearing a hydroxyl group or a fluorine atom attached to benzene ring were comparable to the control doxorubicin with an IC50 value of micro-molar concentration, respectively. It suggests that an azole ring modified with functional side-chain instead of the C-3 carboxylic group is favorable to the improve ment of antitumor activity.

The delivery of therapeutical agents for brain tumors′ treatment is enormously prevented by the presence of blood‐brain barrier .Nano‐carriers such as nano‐particles ,liposomes and micelles can significantly increase the transport of drugs across the blood‐brain barrier .The dual‐targeting nano‐carriers modified by one or two functional groups can further increase the brain delivery of drugs as well as their accumulation in brain tumors ,resulting in significant improvement in the diagnosis and therapy of brain tumors .This article mainly focused on the recent development of strategies and functional groups of dual‐targeting nano‐carriers ,providing a reference for relevant investigations .