Ten new prenylated flavonoids from Macaranga denticulata and their antitumor activities.

Ten new prenylated flavonoids, named denticulains A-J (1-10), together with seven known prenylated flavonoids (11-17) were isolated from Macaranga denticulata. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. In addition, compounds 1 and 14 inhibited the proliferation of SW620 and HCT-116 cell lines with an IC50 value of 46.08 µM and 56.83 µM, respectively.

Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy.

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.

[The relationship between mouth pressure or tracheal pressure and esophagus pressure and diaphragmatic pressure].

OBJECTIVE: To investigate the relationship between mouth pressure (Pmo) or tracheal pressure (Ptr) and esophagus pressure (Pes) or transdiaphragmatic pressure. METHODS: Seventeen patients were involved in the study. Maximal inspiratory pressure (MIP), maximal transdiaphragmatic pressure (Pdi(max)), maximal esophagus pressure (Pes(max)), twitch mouth pressure (TwPmo), twitch transdiaphragmatic pressure (TwPdi) and twitch esophagus pressure (TwPes) were measured before narcotization as a normal procedure for the abdominal operation and twitch tracheal pressure (TwPtr(nar)), twitch esophagus pressure (TwPes(nar)) and twitch transdiaphragmatic pressure (TwPdi(nar)) were dynamically monitored during narcotization. RESULTS: (1) The correlation coefficient (r) values between Pdi(max) and MIP, TwPdi and TwPmo, TwPdi(nar) and TwPtr(nar), Pes(max) and MIP, TwPes and TwPmo, TwPes(nar) and TwPtr(nar) were 0.976 +/- 0.030, 0.816 +/- 0.155, 0.923 +/- 0.446, 0.981 +/- 0.185, 0.829 +/- 0.168 and 0.955 +/- 0.292, respectively. (2) The coefficient variation (CV) of MIP, Pes(max), Pdi(max), TwPmo, TwPes and TwPdi were (14.2 +/- 4.7)%, (15.2 +/- 4.3)%, (15.5 +/- 4.1)%, (30.4 +/- 15.9)%, (10.8 +/- 5.1)% and (9.9 +/- 4.0)%, respectively. The CV of TwPmo was the highest (compare with others, all P < 0.05) and that of TwPes and TwPdi was the lowest (compare with others, all P < 0.05). There was no significant difference among MIP, Pes(max) and Pdi(max) (P > 0.05). (3) The r value between the changing values of TwPtr(nar) and TwPdi(nar) or TwPes(nar) during narcotization were 0.839 or 0.894 (P = 0.000, respectively). CONCLUSION: The measurement of MIP and TwPmo should be repeated and the highest value should be chosen in order to reduce the possibility of underestimating the function of diaphragm, which could be dynamically monitored by TwPtr(nar).