Cardiac safety analysis of first-line chemotherapy drug pegylated liposomal doxorubicin in ovarian cancer.

Pegylated liposomal doxorubicin (PLD) is a nano-doxorubicin anticancer agent. It was used as early as 2014 to treat ovarian and breast cancer, multiple myeloma and Kaposi's sarcoma. The 2018 National Comprehensive Cancer Network guidelines listed PLD as first-line chemotherapy for ovarian cancer. PLD has significant anticancer efficacy and good tolerance. Although PLD significantly reduces the cardiotoxicity of conventional doxorubicin, its cumulative-dose cardiotoxicity remains a clinical concern. This study summarizes the high-risk factors for PLD-induced cardiotoxicity, clinical dose thresholds, and cardiac function testing modalities. For patients with advanced, refractory, and recurrent malignant tumors, the use of PLD is still one of the most effective strategies in the absence of evidence of high risk such as cardiac dysfunction, and the lifetime treatment dose should be unlimited. Of course, they should also be comprehensively evaluated in combination with the high-risk factors of the patients themselves and indicators of cardiac function. This review can help guide better clinical use of PLD.

[Simultaneous Nitrification and Denitrifying Phosphorus Removal in Continuous Flow Reactor with Intermittent Aeration].

A continuous flow reactor (TCFR) with 10 compartments was used to treat domestic sewage. The anaerobic compartments of TCFR were kept at 3. The anoxic compartments of TCFR were reduced from 2 to 0. Therefore, the aerobic compartments of TCFR were increased gradually from 5 to 7. The aerobic compartments were set to continual aeration in Run1 and intermittent aeration from Run2 to Run4. The aeration/non-aeration ratios were 40 min/20 min,40 min/30 min, and 40 min/40 min, respectively. The nitrification liquid reflux ratios were reduced gradually from 150% to 0%. When the average influent concentrations of COD, NH4+-N, TN, and PO43--P were 259.34, 60.26, 64.42, and 6.10 mg·L-1, respectively, the corresponding effluent concentrations were 26.40, 1.03, 5.84, and 0.3 mg·L-1, respectively in Run4. The nitrogen removal amounts increased gradually from 192.30 mg·h-1 in Run1 to 244.00 mg·h-1 in Run4, and the corresponding removal rates increased from 65.40% to 95.30%. The activity of denitrifying phosphorus accumulating organisms (DPAOs) and phosphorus accumulating organisms (PAOs) increased from 36.05% and 38.20% in Run1 to 140.50% and 133.40% in Run4, respectively. Simultaneous nitrification and denitrifying phosphorus removal was achieved in TCFR by adopting intermittent aeration, which provided a reference for the reformation of sewage treatment plants.

[Characteristics of Denitrifying Phosphorus Removal by A2/O-BAF at Low Temperatures].

Low C/N domestic sewage was treated by an A2/O-biological aerated filter (BAF) system at low temperatures (11-14℃). The characteristics of pollutant removal, the ratio of denitrifying phosphorus to nitrogen (ΔPO43-/ΔNO3-N) and effects of aeration flow and effective packing height on nitrification in BAF were studied. The results showed that when the average influent concentrations of COD, NH4+-N, TN and PO43- were 193.1, 58.6, 60.3 and 5.1 mg·L-1 respectively, their effluent concentrations were 46.3, 2.5, 13.4 and 0.3 mg·L-1 respectively, which met the first level A criteria specified in the discharge standard of pollutants for municipal wastewater treatment plant (GB 18918-2002). The linear fitting of ΔPO43-/ΔNO3--N was between 0.47 and 1.75. The normal distribution of mathematical statistics was applied-and the average standard deviation for ΔPO43-/ΔNO3--N were 1.20 and 0.29 respectively. When the aeration flows were 60 L·h-1 and 100 L·h-1, the effluent concentration of NH4+-N was less than 5.0 mg·L-1, corresponding to the effective packing heights in the BAF of 1.8 m and 1.0 m respectively. However, when the aeration flow was increased to 120 L·h-1, the air-water flow led to biofilm detachment, which caused the effluent concentration of NH4+-N to increase beyond 5.0 mg·L-1.

Cytotoxic oxepinochromenone and flavonoids from the flower buds of Rosa rugosa.

A new oxepinochromenone, rugosachromenone A (1), seven new flavonoids, rugosaflavonoids A-G (2-8), and 11 known compounds (9-19) were isolated from the flower buds of Rosa rugosa. Compound 1 is found from Nature for the first time. Compound 2 displayed cytotoxicity against NB4, SHSY5Y, and MCF7 cells with IC50 values of 2.2, 2.5, and 2.3 µM, respectively, and 3 was toxic to A549 and MCF7 cells with IC50 values of 1.2 and 2.8 µM, respectively.

Antiviral phenolic compounds from Arundina gramnifolia.

Five new phenolic compounds, gramniphenols C-G (1-5), and eight known compounds (6-13) were isolated from the whole plant of Arundina gramnifolia. Compounds 1, 4, and 5 showed anti-tobacco mosaic virus activity, with IC(50) values of 20.8, 40.8, and 57.7 µM, respectively. Compounds 1-10 were also tested for their anti-HIV-1 activity; compounds 2, 3, and 6 displayed anti-HIV-1 activity with therapeutic index values above 100:1.

Intestinal permeability of forskolin by in situ single pass perfusion in rats.

The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability.

Isoprenylated flavonoids and adipogenesis-promoting constituents from Morus nigra.

Ten new isoprenylated flavonoids, nigrasins A-J (1-10), and three known compounds were isolated from the twigs of Morus nigra. Compounds 8 and 9 promoted adipogenesis, characterized by increased lipid droplet and triglyceride content in 3T3L1 cells, and induced up-regulation of the expression of adipocyte-specific genes, aP2 and GLUT4.

A fast and sensitive HPLC-MS/MS analysis and preliminary pharmacokinetic characterization of cudratricusxanthone B in rats.

A method for the quantitative analysis of cudratricusxanthone B (CXB) in rat plasma by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) has been developed and validated. The method involved liquid-liquid extraction from plasma, simple chromatographic conditions on a Venusil XBP-PH C(18) column with the mobile phase of 0.5% formic acid in methanol, and mass spectrometric detection using an API-3000 instrument. Multiple reaction monitoring (MRM) mode was used to monitor precursor/product ion transitions of m/z 397.1/285.0 for CXB and m/z 381.6/269.2 for the internal standard (I.S.) cudraxanthone H. The standard curves were linear over the concentration range of 1-500 ng/mL for CXB in rat plasma. The intra- and inter-batch accuracy for CXB at four concentrations was 89.4-99.5% and 89.4-100.8%, respectively. The RSDs were less than 7.92%. The lower limit of quantification for CXB was 1.0 ng/mL using 100 microL of plasma. The average extraction recoveries of CXB ranged from 80.1 to 95.4% at the concentrations of 2, 50 and 500 ng/mL, respectively. This method was successfully applied to the pharmacokinetic study after an intravenous administration of CXB in male Sprague-Dawley (SD) rats.

[Studies on the chemical constituents of Coleus forskohlii].

OBJECTIVE: To study the chemical constituents in the aerial parts of Coleus forskohlii. METHODS: The compounds were isolated by various column chromatographic methods, and their structures were identified by spectroscopic methods. RESULTS: Twelve compounds were isolated and identified as chamaecydin (1), 6 alpha-hydroxydemethylcryptojaponol (2), alpha-cedrene (3), oleanolic acid (4), forskolin G (5), forskolin J (6), 1,6-diacetyl-9-deoxyforskolin (7), forskolin A (8), forskolin H (9), 6-acetyl-1-deoxyforskolin (10), betulinic acid (11), beta-sitosterol (12). CONCLUSION: Compounds 1 - 3 are isolated from Coleus genus for the first time, and compound 4 is isolated from C. forskohlii for the first time.