Comparative evaluation of in vitro and in vivo immunosuppressive potential of cyclosporin g with cyclosporin a and FK-506

Cyclosporin G (CsG), a promising cyclosporin A (CsA) analogue, was examined and compared with two reference immunosuppressive drugs: CsA and FK-506, regarding their inhibitory effects on different lymphocyte activation pathways as well as on graft-versus-host reaction (GvHR) across differences at major or minor histocompatibility loci. The results showed that, at different concentrations, CsG efficiently inhibited proliferation induced by alloantigens (mixed lymphocyte culture), mitogens (concanavalin A, pokeweed mitogen) and the combination of phorbol myristate acetate + ionomycin, to the same extent as observed with CsA and FK-506. It was also shown that CsG exhibited the same strong inhibitory effects as the two other immuno-suppressants upon stimulation triggered by viral (MLs-1^a) or bacterial (staphylococcal enterotoxin B) superantigen. Determination of IL-2 activity in the supernatant of MLC also confirmed similar strong inhibitory effects, exerted by CsG compared to CsA and FK-506. In systemic and local GvHR across major or minor histocompatibility barriers, CsG as well as CsA and FK-506 presented an equivalent immunosuppressive potential. In conclusion, from various experiments involving different modes of activation, it was shown that CsG was as strongly immunosuppressive as CsA and FK-506.     

Retained myoma after laparoscopic supracervical hysterectomy with morcellation

Laparoscopic myomectomy and, more recently, laparoscopic supracervical hysterectomy are practical alternatives to traditional surgical management of uterine fibroids. With the advent of mechanical morcellation these procedures are now much more feasible. A 6-cm fibroid was lost at the time of laparoscopic-assisted supracervical hysterectomy and caused persistent, severe abdominal pain over the next 3 weeks. The fibroid was lodged in the region of the liver and gallbladder and required removal by laparotomy. Although retention of fibroids after operative laparoscopy has been reported, it has not been associated with complications. Technical alternatives at the time of operative laparoscopy involving morcellation should be considered to prevent this event.     

Nanomedicine potentiates mild photothermal therapy for tumor ablation

The booming photothermal therapy (PTT) has achieved great progress in non-invasive oncotherapy, and paves a novel way for clinical oncotherapy. Of note, mild temperature PTT (mPTT) of 42–45 °C could avoid treatment bottleneck of the traditional PTT, including nonspecific injury to normal tissues, vasculature and host antitumor immunity. However, cancer cells can resist mPTT via heat shock response and autophagy, thus leading to insufficient mPTT monotherapy to ablate tumor. To overcome the deficient antitumor efficacy caused by thermo-resistance of cancer cells and mono mPTT, synergistic therapies towards cancer cells have been conducted with mPTT. This review summarizes the recent advances in nanomedicine-potentiated mPTT for cancer treatment, including strategies for enhanced single-mode mPTT and mPTT plus synergistic therapies. Moreover, challenges and prospects for clinical translation of nanomedicine-potentiated mPTT are discussed.     

Effects of triptolide on the sphingosine kinase – Sphingosine-1-phosphate signaling pathway in colitis-associated colon cancer

BackgroundsTriptolide (TP) exhibits effective activity against colon cancer in multiple preclinical models, but the mechanisms underlying the observed effects are not fully understood. Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in the regulation of colon cancer progression. The aim of this study was to investigate the effect of TP on the sphingosine kinase (SPHK)-S1P signaling pathway in colitis-associated colon cancer.MethodsAn azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model and the THP-1 cell line were used to evaluate the therapeutic effects and mechanisms of TP in colitis-associated colon cancer (CACC). Various molecular cell biology experiments, including Western blotting, real-time PCR and immunofluorescence, were used to obtain relevant experimental data. A liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was also established to detect the levels of S1P in tissue and plasma.ResultsIn the AOM/DSS mouse model, TP treatment induced a dose-dependent decrease in tumor incidence and inhibited macrophage recruitment and M2 polarization in the tumors. TP also efficiently decreased the S1P levels and SPHK1/S1PR1/S1PR2 expression and significantly inhibited activation of the S1P-mediated phosphorylation of ERK protein in macrophages.ConclusionsThe results indicated that TP might influence the recruitment and polarization of tumor-associated macrophages by suppressing the SPHK-S1P signaling pathway.     

Immunogenicity and safety of the inactivated enterovirus 71 vaccine administered concomitantly with the measles-rubella vaccine in infants aged 8 months in China: A noninferiority randomized controlled trial

BackgroundTo evaluate the immunogenicity and safety of simultaneous administration of the enterovirus 71 (EV71) vaccine with the measles and rubella (MR) combined vaccine.MethodsIn this phase 4, randomized, open-label and noninferiority study, a total of 680 infants aged 8 months were enrolled and assigned to the simultaneous administration group (infants received the first dose of EV71 vaccine and MR vaccine on Day 0, and the second dose of EV71 vaccine on Day 28), or the separate administration groups (EV71 group: infants received two doses of EV71 vaccine on Day 0 and Day 28, respectively; MR group: infants received MR vaccine on Day 0). Blood sample was obtained on Day 0 and Day 56 to measure antibody responses to each of the antigens in terms of antibody titer or concentration, respectively. Local and systemic adverse reactions (ARs) and other adverse events (AEs) following each dose were monitored and compared among groups.ResultsAfter vaccination, simultaneous administration group showed similar seroconversion rates of antibody against EV71(97.9%), measles (97.4%), and rubella (94.3%) compared to EV71 group (99.6% for anti-EV71) or MR group (98.4% for anti-measles and 98.9% for anti-rubella, respectively). Noninferiority was demonstrated for all antibodies as the lower limits of two-sided 97.5% confidence intervals (CIs) of the difference in seroconversion rates between simultaneous administration group and separate administration groups were above the predefined margin of ?10%. Additionally, the adverse reaction rates were comparable among groups (54.4% in the simultaneous group versus 43.9% in the MR group versus 52.6% in the EV71 group).ConclusionAntibody responses induced by simultaneous administration of EV71 vaccine with MR vaccine were robust and noninferior to those by single administration alone. Like the previous findings by single administration alone, simultaneous administration demonstrated comparable reactogenicity and safety profiles.     

中药鸡骨草的化学成分及其研究近况

中药鸡骨草（Abrus cantoniens Hance）为豆科相思子属植物,具有清热解毒,疏肝止痛之功效,是临床常用中药,亦是我国出口中草药品种之一。我国对这一中药资源的研究和开发工作已进行多年。根据文献报道,综述了近年来有关中药鸡骨草化学成分、药理药效和作用机制以及毒性方面的研究进展。     

雷公藤甲素药代动力学研究进展

雷公藤甲素(TP)作为雷公藤的主要活性成分,具有抗炎、免疫抑制、抗生育、抗囊肿和抗肿瘤等作用,但其治疗窗窄,对消化系统、泌尿生殖系统和血液系统等有较大的毒副作用,因此临床开发研究受到了一定限制.本文主要针对TP药代动力学的研究进行整理和归纳,并概述了基于改善TP体内药动学特性所研发的新型TP衍生物和相关制剂,以期为TP的新药开发研究提供助益.