Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

Baseline Sensitivity and Toxic Action of the Sterol Demethylation Inhibitor Flusilazole Against Botrytis cinerea.

In the present study, a total of 95 Botrytis cinerea single-spore strains collected from different hosts in Shaanxi Province of China were characterized for their sensitivity to the sterol demethylation inhibitor fungicide flusilazole. The effective concentration for 50% inhibition of mycelial growth (EC50) of flusilazole ranged from 0.021 to 0.372 µg/ml, with an average value of 0.093 µg/ml. Cross-resistance between flusilazole and commonly used fungicides was not detected, and no flusilazole-resistant mutants were induced. Both on detached strawberry leaves and in greenhouse experiments, flusilazole was more effective than the commonly used fungicide carbendazim at reducing gray mold. After culture on PDA plates or detached strawberry leaves, no difference in sclerotia production or pathogenicity was detected between two strains, WG12 (most sensitive to flusilazole) and MX18 (least sensitive to flusilazole). After treatment with flusilazole, however, the two strains lost the ability to produce sclerotia, and oxalic acid and ergosterol contents in mycelium decreased. Interestingly, the inhibition rate of ergosterol content in MX18 was significantly lower than that in WG12. Expression of Cyp51, BcatrD, and Bcmfs1 genes all increased after treatment with flusilazole, especially the Cyp51 and BcatrD genes. However, the expression of Cyp51 gene or BcatrD gene in WG12 and MX18 were significantly different from each other after treatment with flusilazole. In addition, no point mutations in Cyp51 gene were found in MX18. These data suggest flusilazole is a promising fungicide for resistance management of gray mold and also provided novel insights into understanding the resistance mechanism of flusilazole against plant pathogens.

Antifungal Activity and Action Mechanism of the Natural Product Cinnamic Acid Against Sclerotinia sclerotiorum.

Sclerotinia stem rot caused by Sclerotinia sclerotiorum (Lib.) de Bary spreads worldwide and causes serious economic losses. Considering the development of fungicide resistance and chemical residues, it is urgently necessary to explore alternative fungicides. In this study, the activity of the natural product cinnamic acid was assessed. The EC50 values for cinnamic acid inhibition of mycelial growth of 103 S. sclerotiorum strains ranged from 9.37 to 42.54 µg/ml with an average EC50 value of 18.77 (±3.39) µg/ml. No cross-resistance was detected between cinnamic acid and the commonly used fungicides carbendazim or dimethachlon. After treatment with cinnamic acid, mycelia distorted with more branches, no sclerotia developed, and the oxalic acid content decreased, whereas cell membrane permeability increased significantly. In pot experiments, cinnamic acid at 2,000 µg/ml provided over 95% efficacy against both carbendazim-sensitive and carbendazim-resistant strains of S. sclerotiorum. The expression of the sclerotia development-correlated genes Sac1, Pac1, Smk1, and Pka1 decreased, whereas the Cna1 gene expression increased. Altogether, cinnamic acid shows potential to be a natural alternative to commercial fungicides or a lead compound to develop new fungicides for the control of Sclerotinia stem rot. The biological characteristics contribute to the understanding of the action mechanism of cinnamic acid against S. sclerotiorum.

Widely targeted metabolomics reveals the antioxidant and anticancer activities of different colors of Dianthus caryophyllus.

Carnation is edible flower that has potent antioxidant properties and is used in traditional Chinese medicinal system and food industry. The phytochemicals responsible for these various proprieties, however, are not fully understood. Thus, in order to recognize metabolite diversity and variability in carnation flowers of different colors and to discover key metabolites that contribute to the differences in antioxidant and anticancer activities, widely targeted LC-MS/MS-based metabolomics analysis was conducted on purple, green, yellow, and white carnation flowers. We identified and chemically categorized 932 metabolites. Metabolic compounds varied significantly with flower color. Several flavonoids, organic acids, phenolic acids, and nucleotides and their derivatives were found to be specific differential metabolites in purple flowers. A total of 128 key differential metabolites were screened. The purple flowers were found to have the highest antioxidant and anticancer activities compared to the other colored flowers. Correlation analysis revealed that the 6-hydroxykaempferol-3,6-O-diglucoside, 6-hydroxykaempferol-7-O-glucoside, quercetin-3-O-sophoroside, and 2'-deoxyguanosine were found to be the major constituents of the antioxidant and anticancer activities. 2'-Deoxyguanosine has effective antiproliferative activity against A549 and U2OS cells for the first report. At the same time, the combination of 2'-deoxyguanosine with 6-hydroxykaempferol-3, 6-O-diglucoside, or quercetin-3-O-sophoroside have also been found to increase the antitumor activity of 2'-deoxyguanosine. These discoveries enrich information on the phytochemical composition of carnation of different colors and provide resources for the overall use and improvement of carnation flowers quality.

[Effects of acrylamide on the permeability of blood cerebrospinal fluid barrier in rats].

OBJECTIVE: To explore the effects of acrylamide on the permeability of blood cerebrospinal fluid barrier (BCB) and tight junction protein ZO-1 of choroid plexus in rats and to provide a theoretical basis for explaining the mechanism of nerve injury induced by acrylamide. METHODS: Thirty two male Sprague-Dawley rats were randomly divided into ACR and control groups. ACR group was exposed to 20 mg/kg ACR daily for 5 days a week by intraperitoneal injection (i.p.) for 4 weeks. Control group was exposed to normal saline. The neurobehavioral tests (including sensatory and motor functions) were performed every week. At the end of exposure, Evan blue (EB) and Sodium fluorescein (NaFI) content in rat CSF were detected for determining the BCB permeability, Real-time PCR was used to measure the expression levels of ZO-1 mRNA in the epithelium cells of choroid plexus, and laser scanning confocal microscope (LSCM) was utilized to observe the distribution of ZO-1 protein. RESULTS: Neurobehavioral tests showed that the tail-flick latencies of ACR group were 27.77% and 53.71% as long as control group in the 3rd week and 4th week, respectively (P < 0.05). The hind lamb splay distances of ACR group were 131.76% and 153.77% as long as control group in the 3rd week and 4th week, respectively (P < 0.05). Evan blue (EB) and Sodium fluorescein (NaFI) content of ACR group were significantly higher than those of control group (P < 0.05). In the 4th week, the expression level of ZO-1 mRNA in ACR group was 0.21 +/- 0.07, which was significantly lower than that (0.31 +/- 0.11) in control group (P < 0.05). In the 4th week, the ZO-1 protein expression level of choroid plexus in ACR group was significantly lower than that in control group (P < 0.05). CONCLUSION: Acrylamide could increased the BCB permeability of rats, which may be involved in the central nervous injury induced by ACR.