Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides / 中国药房

OBJECTIVE To design the two isomers of ferrocene （Fc）-coupled cationic peptides （hereinafter referred to as “peptides”） [Fc-K（C8）FFHK and C8-K（Fc） FFHK] and the control peptide [C8-K（C8）FFHK]， and to explore the effects of Fc position isomerization on the self-assembly behavior and antibacterial effect of peptides. METHODS All isomerized peptides were prepared by standard solid-phase synthesis and purified by reversed-phase high-performance liquid chromatography. The stability of the peptide was analyzed by using UV spectrophotometry to detect UV absorption spectra， and Zeta potential analyzer to determine Zeta potential. The secondary structure was characterized by circular dichroism spectrum （CD）， Fourier transform infrared spectrometer （FTIR）， thioflavin T （ThT） fluorescence spectrum and transmission electron microscopy （TEM）. The differences in antibacterial activity and biocompatibility of the 2 kinds of isomerized peptides were evaluated by in vitro reactive oxygen species （ROS） generation test， growth curve determination test， plate method， cytotoxicity assay and hemolysis test. RESULTS Three peptides with purity higher than 95% were synthesized. The stability test results showed that the UV absorption spectra of Fc-K（C8）FFHK and C8-K（Fc）FFHK remained almost unchanged when placed at room temperature for 24 and 96 hours， and their Zeta potential were decreased by 0.3 mV and 0.5 mV， respectively. Secondary structure characterization results showed that Fc-K（C8）FFHK and C8-K（Fc）FFHK were self-assembled to form twisted nanoribbons and short nanofibers， respectively； C8-K（C8）FFHK was assembled into cylindrical nanofibers. The optical spectrum results showed that there were certain differences in the content of structures such as β-sheet and α-helix. The in vitro ROS generation test results showed that ROS generation efficiency of Fc-K（C8）FFHK at pH 6.0 was higher than C8-K（Fc）FFHK. The results of in vitro antibacterial activity showed that for methicillin-resistant Staphylococcus aureus， both the isomeric peptides had similar minimum inhibitory concentration （MIC） values of 50 μg/mL which were far lower than the control peptide （400 μg/mL）. To Escherichia coli， Fc-K（C8）FFHK had better antibacterial activity than C8-K（Fc）FFHK. Finally， cytotoxicity assay and hemolysis test results showed that both isomeric peptides had good biocompatibility. CONCLUSIONS By wangjingwen8021@163.com coupling Fc， the antibacterial activity of cationic self-assembled peptides can be improved. Regulating the position of Fc in the peptide sequence could regulate the self-assembly behavior and antibacterial effect of the self-assembled peptides.

A dual perspective (conventional and solar-enhanced) on advanced oxidation processes for the treatment of Agave cocui vinasses / Una perspectiva dual (convencional e impulsada por energía solar) sobre procesos de oxidación avanzada para el tratamiento de vinazas de Agave cocui / Uma perspectiva dupla (convencional e aprimorada com energia solar) nos processos de oxidação avançados para tratar vinassas de Agave cocui

Abstract Agave cocui vinasse was physicochemically characterized with reference to the relevant environmental regulations. The following results were obtained: COD: 71,000 mg.L-1, total solids: 21,000 mg.L-1, dissolved solids: 17,000 mg.L-1; pH: 4.06, conductivity: 9.45 mhoscm-1, total Fe: 48.83 mg.L-1, total phenols: 8.66 mg.L-1; BOD: 30,000 mg.L-1. Fenton and photo-Fenton reactions were applied to treat the wastewater produced. For the Fenton process, the optimal oxidation conditions found were pH = 3.48, [COD]:[H2O2] mass ratio = 1:5, and [Fe+2]: [H2O2] mass ratio = 1:6. For the photo-Fenton process, the optimal parameters found were: pH = 3.98, [COD]:[H2O2] = 1:7.86, and [Fe+2]: [H2O2] = 1:5. The experimental data were adjusted to fit second order polynomial models with R2 = 0.88 for the Fenton process and R2 = 0.91 for the photo-Fenton process, respectively. The sludge produced featured the following characteristics: average COD: 41,000 mg.L-1, total Fe: 296,000 mg.L-1, pH: 7.7. The variables with the greatest influence in both processes were [Fe+2]:[H2O2] and [COD]:[H2O2].

Resumen Se caracterizó fisicoquímicamente la vinaza de Agave cocui con base en regulaciones ambientales de referencia. Se obtuvieron los siguientes resultados: DQO: 71 000 mg.L-1, sólidos totales: 21 000 mg.L-1, sólidos disueltos: 17 000 mg.L-1; pH: 4,06, conductividad: 9,45 mhos.cm-1, hierro total: 48,83 mg.L-1, fenoles totales: 8,66 mg.L-1 ; DBO: 30 000 mg.L-1. Se aplicaron las reacciones Fenton y foto Fenton para tratar las aguas residuales producidas. Para el proceso Fenton, las condiciones de oxidación óptimas encontradas fueron pH = 3,48, relación de masa [DQO]:[H2O2] = 1:5 y relación de masa [Fe+2]:[H2O2] = 1:6. Para el proceso foto Fenton, los parámetros óptimos encontraron fueron: pH = 3,98, [DQO]:[H2O2] = 1:7,86 y [Fe+2]:[H2O2] = 1:5. Los datos experimentales fueron ajustados a modelos de segundo orden polinomial con R2 = 0,88 para el proceso Fenton y R2 = 0,91 para el proceso foto Fenton, respectivamente. El lodo producido presentó las siguientes características: DQO promedio: 41 000 mg.L-1, hierro total: 296 000 mg.L-1, pH: 7,7. Las variables con mayor influencia en ambos procesos fueron [Fe+2]:[H2O2] and [DQO]: [H2O2].

Resumo A vinhaça de Agave cocui foi caracterizada físico-quimicamente de acordo com as normas ambientais de referência. Os seguintes resultados foram obtidos: DQO: 71.000 mg.L-1, sólidos totais: 21.000 mg.L-1, sólidos dissolvidos: 17.000 mg.L-1; pH: 4,06, condutividade: 9,45 mhos.cm-1, Fe total: 48,83 mg.L-1, fenóis totais: 8,66 mg.L-1; DBO: 30,000 mg.L-1. As reações de Fenton e foto Fenton foram aplicadas para tratar a água residual produzida. Para o processo Fenton, as condições de oxidação ideais encontradas foram pH = 3,48, razão de massa [DQO]:[H2O2] = 1:5 e razão de massa [Fe+2]:[H2O2] = 1:6. Para o processo de foto Fenton, os parâmetros ideais encontrados foram: pH = 3,98, [DQO]:[H2O2] = 1:7,86 e [Fe+2]:[H2O2] = 1:5. Os dados experimentais foram ajustados para se adequar modelos polinomiais de segunda ordem com R2 = 0,88 para o processo Fenton e R2 = 0,91 para o processo foto Fenton, respectivamente. O lodo produzido apresentou as seguintes características: DQO média: 41.000 mg.L-1, Fe total: 296.000 mg.L-1, pH: 7,7. As variáveis com maior influência em ambos os processos foram [Fe+2]:[H2O2] e [DQO]:[H2O2].

Tumor microenvironments self-activated nanoscale metal-organic frameworks for ferroptosis based cancer chemodynamic/photothermal/chemo therapy

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS

Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name / 基因组蛋白质组与生物信息学报·英文版

It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.

Effect of luxS mutation on the oxidative stress of Streptococcus mutans / 中华微生物学和免疫学杂志

Objective To investigate the effect of luxS inactivation on the oxidative stress of Streptococcus mutans and perform preliminary analysis of potential mechanism.Methods Strains were grown to mid-logarithmic phase and divided into three groups,one was used as control and inoculated into normal TPY medium,and the other two groups were experimental groups,and there were separately inoculated into TPY containing 58.8 mmol/L hydrogen peroxideor TPY containing 58.8 mmol/L hydrogen peroxide and 0.1 mmol/L 2,2'-dipyridyl.The survival rate of strain was calculated at 0.5,1,and 2 h.All the data were statistically analyzed.Results Compared with the control group,the survival rate of luxS mutation was always higher than standard strain at all pre-determined time inexperimental groups (P＜0.05),and compared with experimental group without iron chelator,the survival rate of strains was not raised with the added of iron chelator (P＞0.05).Conclusion luxS gene is involved in oxidative stress tolerance of Streptococcus mutans,and the oxidative stress tolerance is not achieved by avoiding the toxic effects of the Fenton reaction

Hydrogen peroxide induces a specific DNA base change profile in the presence of the iron chelator 2, 2’ dipyridyl in Escherichia coli

Pretreatment of Escherichia coli cultures with the iron chelator 2,2’-dipyridyl (1 mM) protects against the lethal effects of low concentrations of hydrogen peroxide (<15 mM). However, at H2O2 concentrations equal to or greater than 15 mM, dipyridyl pretreatment increases lethality and mutagenesis, which is attributed to the formation of different types of DNA lesions. We show here that pretreatment with dipyridyl (1 mM) prior to challenge with high H2O2 concentrations (≥15 mM) induced mainly G:C→A:T transitions (more than 100X with 15 mM and more than 250X with 20 mM over the spontaneous mutagenesis rate) in E. coli. In contrast, high H2O2 concentrations in the absence of dipyridyl preferentially induced A:T→T:A transversions (more than 1800X and more than 300X over spontaneous mutagenesis for 15 and 20 mM, respectively). We also show that in the fpg nth double mutant, the rpoB gene mutation (RifS-RifR) induced by 20 mM H2O2 alone (20X higher) was increased in 20 mM H2O2 and dipyridyl-treated cultures (110X higher), suggesting additional and/or different lesions in cells treated with H2O2 under iron deprivation. It is suggested that, upon iron deprivation, cytosine may be the main damaged base and the origin of the pre-mutagenic lesions induced by H2O2.

Acute pulmonary responses in vivo to silica complexed with H+, Zn2+, or Fe3+

This investigation is to determine whether the surface complexation of iron influence acute pulmonary responses induced by silica. For this study, three varieties of cation complexed silica were used: silica-H+, -Zn2+, and -Fe3+, since the first two are not active in the transport of electrons and generate little free radicals relative to the dust with the surface iron. Rats (270 to 280 g) were intratracheally (IT) instilled with saline, silica-H+, -Zn2+, or -Fe3+ (5 mg in 0.5 ml saline). After 4 h, cell number, type, and differentiation were analysed in the bronchoalveolar lavage cells, and the levels of lactate dehydrogenase (LDH) and total protein were determined in the lavage fluid. In addition, bronchoalveolar lavage cells were cultured, and nitric oxide production was measured using nitrate assay. Inducible nitric oxide synthase (iNOS) mRNA in the bronchoalveolar lavage cells was also determined by northern blot analysis. Differential counts of the lavage cells showed that red blood cells were increased by 9-, 8-, and 13-fold and total leukocytes (lymphocytes plus polymorphonuclear neutrophils) by 48-, 36-, and 33-fold, following IT silica- H+, -Zn2+, and -Fe3+, respectively compared with the saline group. Meanwhile, there were no significant differences in red blood cells and total leukocytes among any of the cation complexed silica groups. The levels of LDH and total protein in the lavage fluid were significantly increased by 3- to 4-fold. However, compared among these silica groups, Fe3+ complexation did not significantly change the LDH activity and total protein. NO production in cultured bronchoalveolar lavage cells was elevated by 2-fold, following IT any of the silica treatments compared with the saline group. Furthermore, the steady-state levels of iNOS mRNA in the lavage cells were greatly increased. There were any differences in iNOS mRNA expression among the silica-treated groups as with NO production. These findings suggest that surface complexed iron may not influence the acute pulmonary responses resulted from 4h exposure to silica.

Anti-oxidation effects of pyrrolin nitroxides and derivatives in tissues and red blood cell from rats in vitro / 中国药理学通报

AIM To investigate the anti oxidation activities of new systhesized nitroxides in liver, liver mitochondria and RBC from rats and in egg phospholipid. METHODS The homogenates of liver, liver mitochondria from rats and the suspensions of egg phospholipid were used to determine malondialdehyde (MDA) formation induced by Fe 2+ Vit C system using TBA colorimetric method. H 2O 2 caused hemolysis was measured spectrometrically. Superoxide anion was assayed spectrometrically. RESULTS Nitroxides A, B with one active group (NO?) could inhibit MDA generation caused by ?OH generation system significantly, antagonized hemolysis induced by H 2O 2, but did not affect O ? 2 formation; Nitroxide C with two active group (NO?) possessed similar potent anti lipoperoxidative activities,IC 50

MODIFIED METHOD TO EVALUATE THE PROTECTION OF THE ANTIOXIDANTS AGAINST HYDROXYL RADICAL-MEDIATED DNA DAMAGE / 营养学报

Objective To establish a modified method to evaluate the protection of the antioxidant of DNA damage induced by hydroxyl radical. Method Reaction mixture at a final volume of 1.0 ml contained 0.8mg/ml DNA,0.2 mmol/L H2O2,1.0 mmol/L ascorbic acid,in 50 mmol/L NaH2PO4-Na2HPO4 buffer (pH 7.4). EDTA(1.0 mmol/L) and FeCl2 (1.0 mmol/L)were premixed and then dispensed into the reaction mixture to trigger the Fenton reaction,and the mixture was incubated at 37℃ for 30 min. The reaction was stopped by dispensing 1ml of 10% (w/v) trichloroacetic acid ,and reaction mixture was mixed with 1ml of 1% (w/v) 2-thiobarbituric acid,then further heated at 80 ℃ for 30 min. The chromogen formed was extracted into n-1-butanol and absorbance was measured at 532 nm. Results Addition of hydroxyl radical scavenger can compete with DNA for the hydroxyl radicals and diminished TBARS formation at a defined time of reaction with dose-dependent effect. The result showed that hydroxyl radical scavenger exerted inhibition effects on hydroxyl radical-mediated DNA damage. Conclusion This method can be used to evaluate the protection of the antioxidant of DNA damage induced by hydroxyl radical.