An ethanol extract of the stem of Opuntia ficus-indica var. saboten (OFS) was assessed to determine the mechanism(s) of its antioxidant activity. The ethanol extract exhibited a concentration-dependent inhibition of linoleic acid oxidation in a thiocyanate assay system. In addition, the OFS extract showed dose-dependent free-radical scavenging activity, including DPPH radicals, superoxide anions (O(2)(*-)), and hydroxyl radicals (*OH), using different assay systems. The OFS ethanol extract was also found to be effective in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals in a Fenton's reaction mixture. Furthermore, the extract showed significant (p < 0.01) dose-dependent protection of mouse splenocytes against glucose oxidase-mediated cytotoxicity. Finally, the OFS extract was characterized as containing a high amount of phenolics (180.3 mg/g), which might be the active compounds responsible for the antioxidant properties of the OFS extract.

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Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment.This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11) or both, either sequentially (n=10) or in coadministration (n=1), for >1 month, combined with a World Health Organization-recommended regimen.Of these, 49 (80.3%) were male and 12 (19.7%) were female. The median (interquartile range (IQR)) age was 53 (38.5-61.0) years. 42 (68.9%) patients had fluoroquinolone-resistant MDR-TB and 16 (26.2%) had extensively drug-resistant TB. The median (IQR) duration of treatment with bedaquiline and/or delamanid was 168 (166.5-196.5) days, with 33 (54.1%) receiving linezolid for a median (IQR) of 673 (171-736) days. Of the 55 patients with positive sputum cultures at the start of bedaquiline and/or delamanid treatment, 39 (70.9%) achieved sputum culture conversion within a median of 119 days. Treatment was halted in four patients (6.6%) because of prolonged Fridericia's corrected QT interval.Bedaquiline and delamanid were effective and safe for treating MDR-TB, with initial evidence of sequential administration of these two drugs as a viable treatment strategy for patients when an adequate treatment regimen cannot be constructed.

BackgroundShikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, induces necroptosis in various cancer types, but the mechanisms underlying the anticancer activity of shikonin in lung cancer are not fully understood. This study was designed to clarify whether shikonin causes necroptosis in non-small cell lung cancer (NSCLC) cells and to investigate the mechanism of action.MethodsMultiplex and caspase 8 assays were used to analyze effect of shikonin on A549 cells. Cytometry with annexin V/PI staining and MTT assays were used to analyze the mode of cell death. Western blotting was used to determine the effect of shikonin-induced necroptosis and autophagy. Xenograft and orthotopic models with A549 cells were used to evaluate the anti-tumor effect of shikonin in vivo.ResultsMost of the cell death induced by shikonin could be rescued by the specific necroptosis inhibitor necrostatin-1, but not by the general caspase inhibitor Z-VAD-FMK. Tumor growth was significantly lower in animals treated with shikonin than in the control group. Shikonin also increased RIP1 protein expression in tumor tissues. Autophagy inhibitors, including methyladenine (3-MA), ATG5 siRNA, and bafilomycin A, enhanced shikonin-induced necroptosis, whereas RIP1 siRNA had no effect on the apoptotic potential of shikonin.ConclusionsOur data indicated that shikonin treatment induced necroptosis and autophagy in NSCLC cells. In addition, the inhibition of shikonin-induced autophagy enhanced necroptosis, suggesting that shikonin could be a novel therapeutic strategy against NSCLC.

Paraquat-induced pulmonary fibrosis involves two factors, direct injury by oxygen free radicals and indirect injury by inflammatory cells and fibroblasts. Endothelin-1 (ET-1) has been shown to act as a mediator of pulmonary fibrosis, and its formation increases during oxidative stress. We investigated whether green tea extract (GTE), which has antioxidant properties, inhibits paraquat-induced pulmonary fibrosis and whether ET-1 is involved in this process. Paraquat (0.3 mg/kg) was instilled into the right lungs of rats, following which the rats were either not further treated (Group P, n = 7), or they were administered 1% GTE mixed with feed (Group PG; n = 7) or the ET(A) receptor antagonist ZD2574 (10 mg/kg through gavage; Group PZ; n = 7) for two weeks. As control, we used rats instilled with saline (Group N; n = 6). Two weeks after paraquat instillation, we assayed the degree of pulmonary fibrosis by light microscopic morphometry and hydroxyproline content; lipid peroxidation as a marker of oxidative stresses by measurement of malondialdehyde (MDA); ET-1 by immunohistochemistry; and prepro-ET-1 mRNA expression by reverse transcription-polymerase chain reaction. Compared with Group N, significant pulmonary fibrosis was observed in Group P, accompanied by increases in MDA, ET-1, and prepro-ET-1 mRNA expression. Compared with Group P, Group PG showed significant decreases in pulmonary fibrosis, along with decreases in MDA, ET-1, and prepro-ET-1 mRNA expression. We also observed significant decreases in pulmonary fibrosis in Group PZ compared with Group P. These findings suggest that GTE inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and ET-1 expression.