Leukotriene B₄ (LTB₄) is a proinflammatory lipid mediator that is synthesized by a number of inflammatory cells. Binding of LTB₄ to its receptor leukotriene B₄ receptor 1 (BLT1) can migrate neutrophils and macrophages to inflammatory sites through chemotaxis and up-regulation of adhesion molecules. Many researches have shown that LTB₄-BLT1 axis is related to the occurrence of autoimmune disorders and other inflammatory diseases. Receptor antagonists of LTB₄ are thus expected to be useful therapeutics for these diseases. In this review, we briefly describe the biological function of LTB₄ and summarize the preclinical and clinical developments of LTB₄ receptor antagonists.

Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Cell Division ; drug effects ; Colchicine ; analogs & derivatives ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Structure-Activity Relationship ; Tubulin ; drug effects ; Tumor Cells, Cultured

Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Camptothecin ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Structure-Activity Relationship ; Topotecan ; chemistry ; therapeutic use ; Tumor Cells, Cultured ; drug effects

OBJECTIVETo investigate the effect of the overexpression of the ERbeta gene on the penile vascular endothelium of ERbeta knockout (ERbetaKO) mice and its molecular mechanisms.

METHODSWe randomly divided 12 ERbetaKO male mice into groups A (ERbetaKO + TNFalpha + pAdxsi-ERbeta) and B (ERbetaKO + TNFalpha + empty virus), the former treated by pAdxsi-ERbeta adenovirus transfection, the latter with empty virus, and meanwhile both injected intraperitoneally with TNFalpha at 6 microg per kg body weight per d for 14 days. Then we observed the erectile function of the mice by APO, determined the changes of the endothelial markers CD34 and vWF by immunohistochemical staining, and detected the expressions of the relevant molecules in the eNOS-NO pathway by RT-PCR, Western blot and immunohistochemistry.

RESULTSCompared with group B, group A showed a significantly increased number of penile erections (0.50 +/- 0.55 vs 2.17 +/- 0.41, P < 0.05), shortened erectile latency ([28.83 +/- 1.33] min vs [24.00 +/- 1.27] min, P < 0.05), enriched CD34 and vWF markers (0.67 +/- 0.52 vs 1.50 +/- 0.55 and 0.50 +/- 0.55 vs 1.33 +/- 0.52, both P < 0.05), elevated expressions of eNOS and Cam (RT-PCR: 1.38 +/- 0.03 vs 1.62 +/- 0.05 and 1.02 +/- 0.09 vs 1.42 +/- 0.05, both P < 0.05; Western blot: 1.27 +/- 0.04 vs 1.55 +/- 0.07 and 0.76 +/- 0.05 vs 0.95 +/- 0.08, both P < 0.05), and reduced expression of caveolin-1 (RT-PCR: 2.13 +/- 0.13 vs 1.72 +/- 0.08, P < 0.05; Western blot: 3.99 +/- 0.16 vs 3.40 +/- 0.14, P < 0.05). The results of RT-PCR were consistent with those of Western blot.

CONCLUSIONThe ERbeta gene protects the penile vascular endothelium via the eNOS-NO pathway.

Adenoviridae ; genetics ; Animals ; Endothelium, Vascular ; metabolism ; Estrogen Receptor beta ; genetics ; Male ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Penis ; blood supply ; metabolism ; Transfection

OBJECTIVE Evidience appears that parthenolide (PN) induces anti-tumor effects by NF-κB signal pathway. MCL3 the derivative of PN,is sesquiterpene lactone synthesized by the group of Professor Pan Xiandao.The study was to explore the anti-tumor activity and mechanism of MCL3 in glioma. METHODS The effect of MCL3 on the proliferation of glioma cell lines was examined by MTT assay. Apoptotic activity was investigated by flow cytometry. The Transwell cell invasion assay was used to determine the effect of MCL3 on the G422 cell invasive ability.The effect of MCL3 on the angio-genesis was analyzed by a capillary-like tube formation assay. The subcutaneously transplanted and orthotopic G422 cell xenograft models were used to detect the effect of MCL3 on tumor growth in vivo. The pathological changes were analyzed by H&E staining. Protein level related to the NF-κB signal pathway was dertimined by Western blotting. The effect of MCL3 on the NF-κB transcriptional activity was examined by a dual-luciferase reporter assay.RESULTS The anti-proliferative activity was observed following treatment with MCL3 for 96 h in G422, U-87 MG, U251 and Hs683 cell lines, and the IC50 was 8.94 μmol·L-1,6.44 μmol·L-1,14.8 μmol·L-1,18.9 μmol·L-1,respectively.The percentage of apop-totic cells increased in MCL3-treated G422 cells,and the apoptosis rate was 26.4%(the apoptosis rate was 5.68% in control group).MCL3 could inhibit the invasion in G422 cells,and the invasive inhibition rate was 43.63%(P<0.01)at 10.0 μmol·L-1.MCL3 inhibited tube formation of EA.hy926 cells,and the inhibitory rate was 81.67%(P<0.01)at 10.0 μmol·kg-1.At 40.00 mg·kg-1,MCL3 supressed tumor growth by 79.03% (P<0.01) in tumor weight in subcutaneously transplanted G422 xenograft models, and by 69.97% (P<0.01) in volume in orthopotic G422 xenograft models. H&E staining demonstrated that MCL3 could decrease tumor angiogenesis and invasion, increased necrosis of tumor cells. The dual-luciferase reporter assay showed that MCL3 inhibited NF-κB transcriptional actvity, and the inhibition rate was 50.07%(P<0.05)at 10.0 μmol·L-1compared with control.Moreover,MCL3 inhibited the phos-phorylation of NF-κB in nuclear mediated by supression of phosphorylated IKKα/β and IκB,and decreased the expression of IL-6 regulated by NF-κB.Eventually,the phosphorylation of State3 decreased following the administration of MCL3, resulting in the downregulation of State3 taget genes, including HIF, VEGF,FAK,MMP-2,MMP-9,Bcl-2 and Bcl-xL.CONCLUSION The anti-tumor effect of MCL3 was partly due to the inhibition of NF-κB/IL-6/State3 pathway in glioma.

AIMTo improve the biological activity of A-ring modified analogues of camptothecin.

METHODSA-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo antitumnor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds.

CONCLUSIONThe modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of A-ring will reduce the antitumor activity of camptothecins.

Animals ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Line, Tumor ; drug effects ; Female ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Mice ; Neoplasm Transplantation ; Polycyclic Compounds ; chemical synthesis ; pharmacology

AIMTo improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed.

METHODSThese derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice.

RESULTSTwelve derivatives of camptothecin ester are new compounds.

CONCLUSIONIn vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Esters ; chemistry ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred ICR ; Molecular Structure ; Neoplasm Transplantation ; Topotecan ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

AIMTo search for colchicine derivatives which have high efficacy and low toxicity.

METHODSColchicine was firstly converted into thiocolchicine, and then it was hydrolyzed to get 7-(N-deacetylthiocolchicine). At last, 7-(N-deacetylthiocolchicine) was amidated to get the target compounds. The chemical structure of these new derivatives was confirmed with 1H NMR, IR, MS, and HR-MS. The cytotoxicity of the compounds was tested by MTT assay. Their in vivo antitumor activity was evaluated against mice tumor H22 and U14.

RESULTSTwelve thiocolchicine derivatives are new compounds.

CONCLUSIONIn vitro antitumor activity has showed that some of these thiocolchicines possessed cytotoxic activity superior to colchicine. However, in vivo antitumor activity indicated that these derivatives have poor efficacy in mice.

Animals ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Colchicine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms, Experimental ; pathology ; prevention & control ; Male ; Mice ; Mice, Inbred ICR ; Models, Chemical ; Molecular Structure ; Neoplasm Transplantation ; Prostatic Neoplasms ; pathology ; prevention & control ; Structure-Activity Relationship

Ellipticine is an alkaloid isolated from natural product with cytotoxicity, which has antitumor and anti-aids activity. Since it was first identified in 1959, a great deal of effort has been devoted to the development of various approaches for synthesis of ellipticine. This review provides a summary for synthesis approaches of ellipticine from different starting materials. The antitumor mechanism and structure-activity relationship are also discussed.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.