pH dependence of charge transfer between tryptophan and tyrosine in dipeptides

Time-resolved absorption spectroscopy has been employed to study the directionality and rate of charge transfer in W-Y and Ac-W-Y dipeptides as a function of pH. Excitation with 266-nm nanosecond laser pulses produces both W⋅ (or [⋅WH]⁺, depending on pH) and Y⋅. Between pH 6 and 10, W⋅ to was found to oxidize Y with k_X⋅=9.0×10⁴ s⁻¹ and 1.8×10⁴ s⁻¹ for the W-Y and Ac-W-Y dipeptide systems, respectively. The intramolecular charge transfer rate increases as the pH is lowered over the range 6>pH>2. For 10<pH<12, the rate of radical transport for the W-Y dipeptide decreases and becomes convoluted with other radical decay processes, the timescales of which have been identified in studies of control dipeptides Ac-F-Y and W-F. Further increases in pH prompt the reverse reaction to occur, W-Y⋅→W⋅-Y⁻ (Y⁻, tyrosinate anion), with a rate constant of k_X⋅=1.2×10⁵ s⁻¹. The dependence of charge transfer directionality between W and Y on pH is important to the enzymatic function of several model and natural biological systems as discussed here for ribonucleotide reductase.     

Aromatase inhibitory, radical scavenging, and antioxidant activities of depsidones and diaryl ethers from the endophytic fungus Corynespora cassiicola L36

Isolation of a broth extract of the endophytic fungus Corynespora cassiicola L36 afforded three compounds, corynesidones A (1) and B (3), and corynether A (5), together with a known diaryl ether 7. Compounds 1, 3, 5, and 7 were relatively non-toxic against cancer cells, and inactive toward normal cell line, MRC-5. Corynesidone B (3) exhibited potent radical scavenging activity in the DPPH assay, whose activity was comparable to ascorbic acid. Based on the ORAC assay, compounds 1, 3, 5, and 7 showed potent antioxidant activity. However, the isolated natural substances and their methylated derivatives (1−8) neither inhibited superoxide anion radical formation in the XXO assay nor suppressed TPA-induced superoxide anion generation in HL-60 cell line. Corynesidone A (1) inhibited aromatase activity with an IC₅₀ value of 5.30 μM.     

Emergence and transmission of visual awareness through optical coding in the brain: A redox molecular hypothesis on visual mental imagery

Does the primary visual cortex mediate consciousness for higher-level stages of information processing by providing an outlet for mental imagery? Evidence based on neural electrical activity is inconclusive as reflected in the “imagery debate” in cognitive science. Neural information and activity, however, also depend on regulated biophoton (optical) signaling. During encoding and retrieval of visual information, regulated electrical (redox) signals of neurons are converted into synchronized biophoton signals by bioluminescent radical processes. That is, visual information may be represented by regulated biophotons of mitochondrial networks in retinotopically organized cytochrome oxidase-rich neural networks within early visual areas. Therefore, we hypothesize that regulated biophotons can generate intrinsic optical representations in the primary visual cortex and then propagate variably degraded versions along cytochrome oxidase pathways during both perception and imagery. Testing this hypothesis requires to establish a methodology for measurement of in vivo and/or in vitro increases of biophoton emission in humans' brain during phosphene inductions by transcranial magnetic stimulation and to compare the decrease in phosphene thresholds during transcranial magnetic stimulation and imagery. Our hypothesis provides a molecular mechanism for the visual buffer and for imagery as the prevalent communication mode (through optical signaling) within the brain. If confirmed empirically, this hypothesis could resolve the imagery debate and the underlying issue of continuity between perception and abstract thought.     

Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants

Traditional Chinese medicinal plants associated with anticancer contain a wide variety of natural phenolic compounds with various structural features and possessing widely differing antioxidant activity. The structure-radical scavenging activity relationships of a large number of representative phenolic compounds (e.g., flavanols, flavonols, chalcones, flavones, flavanones, isoflavones, tannins, stilbenes, curcuminoids, phenolic acids, coumarins, lignans, and quinones) identified in the traditional Chinese medicinal plants were evaluated using the improved ABTS*+ and DPPH methods. Different categories of tested phenolics showed significant mean differences in radical scavenging activity. Tannins demonstrated the strongest activity, while most quinones, isoflavones, and lignans tested showed the weakest activity. This study confirmed that the number and position of hydroxyl groups and the related glycosylation and other substitutions largely determined radical scavenging activity of the tested phenolic compounds. The differences in radical scavenging activity were attributed to structural differences in hydroxylation, glycosylation and methoxylation. The ortho-dihydroxy groups were the most important structural feature of high activity for all tested phenolic compounds. Other structural features played a modified role in enhancing or reducing the activity. Within each class of phenolic compounds, the structure-activity relationship was elucidated and discussed. This study reveals the structure-activity relationships of a large series of representative natural phenolic compounds more systematically and fully than previous work. Structure-radical scavenging activity relationships of some natural phenolics identified in the medicinal plants were evaluated for the first time.     

Design,synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer’s disease therapy

A series of novel 2-methoxy-phenyl dimethyl-carbamate derivatives were designed, synthesized and evaluated as site-activated MTDLs based on rivastigmine and curcumin. Most of them exhibited good to excellent AChE and BuChE inhibitory activities with sub-micromolar IC₅₀ values. Among all the compounds, 6a demonstrated the most potent AChE inhibition with IC₅₀ value of 0.097 μM, which is about 20-fold than that of rivastigmine. In addition, the three selected compounds 5a, 6a and 6e demonstrated inhibitory activity against Aβ self-aggregation similar to cucurmin in TEM assay, which is obviously different from the weak activity of rivastigmine. Moreover, the hydrolysate of 6a (compound 7) also showed potent ABTS⁺ scavenging and moderate copper ion chelating activity in vitro.     

Organochalcogen compounds from glycerol: Synthesis of new antioxidants

We describe here a simple method for the synthesis of glycerol derivatives containing an organochalcogen unit (Se, Te and S) using NaBH₄ and PEG-400 as a solvent. The new methodology was used to synthesize a range of new organochalcogen compounds in good yields. Furthermore, four of synthesized compounds were evaluated for their antioxidant activity using different assays, such as 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, nitric oxide (NO) and hydroxyl radical (OH) scavenging, ferric ion reducing antioxidant power (FRAP), ferrous ion chelating, superoxide dismutase-like activity and inhibition of linoleic acid lipid peroxidation. The new organotellurium 2,2-dimethyl-4-(phenyltellanylmethyl)-1,3-dioxolane 3j showed antioxidant activity and was more effective in inhibition of induced lipid peroxidation compared to solketal 4. Selenium and sulfur analogs 3a and 3m and solketal 4 did not present antioxidant effect. These findings suggest that 2,2-dimethyl-4-(phenyltellanylmethyl)-1,3-dioxolane 3j is a promising antioxidant and that its activity is influenced by the presence of the tellurium atom on the structure.     

Multiple Glycosaminoglycan-binding Epitopes of Monocyte Chemoattractant Protein-3/CCL7 Enable It to Function as a Non-oligomerizing Chemokine

The interaction of chemokines with glycosaminoglycans (GAGs) facilitates the formation of localized chemokine gradients that provide directional signals for migrating cells. In this study, we set out to understand the structural basis and impact of the differing oligomerization propensities of the chemokines monocyte chemoattractant protein (MCP)-1/CCL2 and MCP-3/CCL7 on their ability to bind GAGs. These chemokines provide a unique comparison set because CCL2 oligomerizes and oligomerization is required for its full in vivo activity, whereas CCL7 functions as a monomer. To identify the GAG-binding determinants of CCL7, an unbiased hydroxyl radical footprinting approach was employed, followed by a focused mutagenesis study. Compared with the size of the previously defined GAG-binding epitope of CCL2, CCL7 has a larger binding site, consisting of multiple epitopes distributed along its surface. Furthermore, surface plasmon resonance (SPR) studies indicate that CCL7 is able to bind GAGs with an affinity similar to CCL2 but higher than the non-oligomerizing variant, CCL2(P8A), suggesting that, in contrast to CCL2, the large cluster of GAG-binding residues in CCL7 renders oligomerization unnecessary for high affinity binding. However, the affinity of CCL7 is more sensitive than CCL2 to the density of heparan sulfate on the SPR surfaces; this is likely due to the inability of CCL7 to oligomerize because CCL2(P8A) also binds significantly less tightly to low than high density heparan sulfate surfaces compared with CCL2. Together, the data suggest that CCL7 and CCL2 are non-redundant chemokines and that GAG chain density may provide a mechanism for regulating the accumulation of chemokines on cell surfaces.     

瑞芬太尼靶控输注对宫颈癌根治术患者麻醉苏醒质量、应激反应及Th1/Th2免疫平衡的影响

摘要 目的：观察瑞芬太尼靶控输注对宫颈癌根治术患者麻醉苏醒质量、应激反应及辅助T细胞（Th）1/Th2免疫平衡的影响。方法：按照随机数字表法将2023年1月到2023年6月期间我院接受的120例宫颈癌根治术患者分为舒芬太尼组（n=60,舒芬太尼麻醉）和瑞芬太尼组（n=60,瑞芬太尼麻醉）。对比两组的麻醉苏醒质量、应激反应指标[皮质醇（Cor）、去甲肾上腺素（NE）、血管紧张素1（Ang-1）、血管紧张素2（Ang-2）]、Th1/Th2免疫平衡指标[包括Th1、Th2及调节性T细胞（Treg）、Th1/Th2比值],术后记录不良反应发生情况。结果：与舒芬太尼组相比,瑞芬太尼组的应激呼吸恢复时间、睁眼时间、拔管时间更短（P<0.05）。术后1 d,两组Cor、NE、Ang-1、Ang-2升高,但瑞芬太尼组低于舒芬太尼组（P<0.05）。术后1 d,两组Th1、Treg、Th1/Th2升高,但瑞芬太尼组低于舒芬太尼组;Th2下降,但瑞芬太尼组高于舒芬太尼组（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。结论：瑞芬太尼靶控输注用于宫颈癌根治术患者,可改善麻醉苏醒质量,减轻应激反应,调节Th1/Th2免疫平衡,且不增加不良反应的发生率,效果较好。     

Alterations of human erythrocyte membrane fluidity by oxygen-derived free radicals and calcium

Two possible reasons for the structural alterations of cell membranes caused by free radicals are lipid peroxidation and an increase in the intracellular calcium ion concentration. To characterize the alterations in membrane molecular dynamics caused by oxygen-derived free radicals and calcium, human erythrocytes were spin-labeled with 5-doxyl stearic acid, and alterations in membrane fluidity were quantified by electron spin resonance oxidase (0.07 U/mL) decreased membrane fluidity, and the addition of superoxide dismutase and catalase inhibited the effect on membrane fluidity of the hypoxanthine-xanthine oxidase system. Hydrogen peroxide (0.1 and 1 nM) also decreased membrane fluidity and caused alterations to erythrocyte morphology. In addition, a decrease in membrane fluidity was observed in erythrocytes incubated with 2.8 mM CaCl₂. On the other hand, incubation of erythrocytes with calcium-free solution decreased the changes in membrane fluidity caused by hydrogen peroxide.

These results suggest that changes in membrane fluidity are directly due to lipid peroxidation and are indirectly the result of increased intracellular calcium concentration. We support the hypothesis that alterations of the biophysical properties of membranes caused by free radicals play an important role in cell injury, and that the accumulation of calcium amplifies the damge to membranes weakened by free radicals.