Molecular mechanisms of bufadienolides and their novel strategies for cancer treatment.

Bufadienolides are cardioactive C24 steroids with an α-pyrone ring at position C17. In the last ten years, accumulating studies have revealed the anticancer activities of bufadienolides and their underlying mechanisms, such as induction of autophagy and apoptosis, cell cycle disruption, inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and stemness, and multidrug resistance reversal. As Na+/K+-ATPase inhibitors, bufadienolides have inevitable cardiotoxicity. Short half-lives, poor stability, low plasma concentration and oral bioavailability in vivo are obstacles for their applications as drugs. To improve the drug potency of bufadienolides and reduce their side effects, prodrug strategies and drug delivery systems such as liposomes and nanoparticles have been applied. Therefore, systematic and recapitulated information about the antitumor activity of bufadienolides, with special emphasis on the molecular or cellular mechanisms, prodrug strategies and drug delivery systems, is of high interest. Here, we systematically review the anticancer effects of bufadienolides and the molecular or cellular mechanisms of action. Research advancements regarding bufadienolide prodrugs and their tumor-targeting delivery strategies are critically summarized. This work highlights recent scientific advances regarding bufadienolides as effective anticancer agents from 2011 to 2019, which will help researchers to understand the molecular pathways involving bufadienolides, resulting in a selective and safe new lead compound or therapeutic strategy with improved therapeutic applications of bufadienolides for cancer therapy.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS.

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg-1 of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

A microbial model of mammalian metabolism: biotransformation of 4,5-dimethoxyl-canthin-6-one using Cunninghamella blakesleeana CGMCC 3.970.

1. A filamentous fungus, Cunninghamella blakesleeana CGMCC 3.970, was applied as a microbial system to mimic mammalian metabolism of 4,5-dimethoxyl-canthin-6-one (1). Compound 1 belongs to canthin-6-one type alkaloids, which is a major bioactive constituent of a traditional Chinese medicine (the stems of Picrasma quassioides). 2. After 72 h of incubation in potato dextrose broth, 1 was metabolized to seven metabolites as follows: 4-methoxyl-5-hydroxyl-canthin-6-one (M1), 4-hydroxyl-5-methoxyl-canthin-6-one (M2), canthin-6-one (M3), canthin-6-one N-oxide (M4), 10-hydroxyl-4,5-dimethoxyl-canthin-6-one (M5), 1-methoxycarbonl-ß-carboline (M6), and 4-methoxyl-5-O-ß-D-glucopyranosyl-canthin-6-one (M7). 3. The structures of metabolites were determined using spectroscopic analyses, chemical methods, and comparison of NMR data with those of known compounds. Among them, M7 was a new compound. 4. The metabolic pathways of 1 were proposed, and the metabolic processes involved phase I (O-demethylation, dehydroxylation, demethoxylation, N-oxidation, hydroxylation, and oxidative ring cleavage) and phase II (glycosylation) reactions. 5. This was the first research on microbial transformation of canthin-6-one alkaloid, which could be a useful microbial model for producing the mammalian phase I and phase II metabolites of canthin-6-one alkaloids. 6. 1, M1-M5, and M7 are canthin-6-one alkaloids, whereas M6 belongs to ß-carboline type alkaloids. The strain of Cunninghamella blakesleeana can supply an approach to transform canthin-6-one type alkaloids into ß-carboline type alkaloids.

Total date rate of multi-wavelength 2R regenerators for time-interleaved RZ-OOK signals.

Multi-wavelength regeneration free of inter-channel crosstalk is desirable for wavelength division multiplexing (WDM) systems, especially from the cost-effectiveness point of view. This paper presents the design rules of time-interleaved multi-wavelength 2R regeneration systems based on data-pump four wave mixing (FWM) effect, and several key factors, such as FWM bandwidth, wavelength assignment, and duty cycle, are comprehensively taken into account. The total data rate of time-interleaved WDM regeneration systems along with polarization multiplexing or bidirectional transmission are discussed, which are mainly determined by temporal overlap, spectral broadening and FWM bandwidth. As two examples, an eight-wavelength unidirectional regenerator using polarization multiplexing is designed by optimizing the fiber birefringence, and a six-wavelength bidirectional regenerator is demonstrated by experiment. Each is expected to have a total data rate of about 200 Gb/s for the optical RZ-OOK signals, and the wavelength number is increased at the expense of spectral efficiency.

All-fiber magneto-optic Sagnac interferometer.

An all-fiber magneto-optic Sagnac interferometer (AFMOSI) utilizing intrinsic Faraday effects in highly nonlinear fibers (HNLFs) is presented for the first time (to our knowledge). The performance of the AFMOSI was investigated theoretically by use of the transfer matrix approach. The theoretical results were verified by the experiment employing an all-fiber magnetic-optic cell that consists of a 30 m long HNLF and a 92 mm diameter toroid coil. Our experiments show that, when the linear birefringence of the AFMOSI is adjusted to 0, the change of the transmission can be over 10 dB as the magnetic induction B increases from 0 to 180 Gs. The sensitivity of the AFMOSI is determined by the coupling ratio of the fiber coupler, the loss of the loop, and the length of the HNLF. Most importantly, the linear birefringence of the AFMOSI can be obtained by evaluating its performance of magnetic field response. This is very useful for studying the influence of the linear birefringence on the performance of a nonlinear optical loop mirror that is controlled by the Faraday effect.