Coordination-assembled Nanoarchitectonics of Antioxidant Peptide and Flavonoid Myricetin for Sustainably Scavenging Free Radicals

Oxidative stress can lead to permanent and irreversible damage for cellular components, and even cause cancer and many diseases. Therefore, the development of antioxidative reagents is a significant strategy for alleviating chronic diseases and maintaining the redox balance. Small-molecule bioactive compounds have exhibited huge therapeutic potential in antioxidant and anti-inflammatory. Myricetin (Myr) as well-defined natural flavonoid, has drawn wide attention on highly effective antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Especially at antioxidation, Myr is capable of not only chelating intracellular transition metal ions for removing reactive oxygen species (ROS), but also activating antioxidant enzymes and related signal, achieving sustainable scavenging radical activity. However, Myr possesses poor water solubility, which limits its bioavailability for biomedical application, even clinical therapeutic potential. The endogenous antioxidant peptide glutathione (GSH) plays a direct role on antioxidant in cells and possesses good hydrophilicity and biocompatibility, but is easily metabolized by enzyme. To take advantages of their antioxidation activity and overcome the above-mentioned limitations, the GSH, Zn2+ and Myr are selected to co-assemble into Myr-Zn2+-GSH (abbreviated as MZG nanoparticles or nanoarchitectonics). Thence, this study offers a new design to harness stable, sustainable antioxidant nanoparticles with high loading capacity and bioavailability, good biocompatibility for optimizing antioxidant to protect cells from oxygenated damage.

Melatonin Attenuates Ischemia/Reperfusion-Induced Oxidative Stress by Activating Mitochondrial Fusion in Cardiomyocytes

Myocardial ischemia/reperfusion (I/R) injury can stimulate mitochondrial reactive oxygen species production. Optic atrophy 1- (OPA1-) induced mitochondrial fusion is an endogenous antioxidative mechanism that preserves the mitochondrial function. In our study, we investigated whether melatonin augments OPA1-dependent mitochondrial fusion and thus maintains redox balance during myocardial I/R injury. In hypoxia/reoxygenation- (H/R-) treated H9C2 cardiomyocytes, melatonin treatment upregulated OPA1 mRNA and protein expression, thereby enhancing mitochondrial fusion. Melatonin also suppressed apoptosis in H/R-treated cardiomyocytes, as evidenced by increased cell viability, diminished caspase-3 activity, and reduced Troponin T secretion; however, silencing OPA1 abolished these effects. H/R treatment augmented mitochondrial ROS production and repressed antioxidative molecule levels, while melatonin reversed these changes in an OPA1-dependent manner. Melatonin also inhibited mitochondrial permeability transition pore opening and maintained the mitochondrial membrane potential, but OPA1 silencing prevented these outcomes. These results illustrate that melatonin administration alleviates cardiomyocyte I/R injury by activating OPA1-induced mitochondrial fusion and inhibiting mitochondrial oxidative stress.

Effects of daytime ingestion of melatonin on heart rate response during prolonged exercise

The current study sought to investigate the effect of melatonin consumption on cardiovascular response during submaximal exercise in healthy men. For this purpose, eight students (age: 21.8 ± 0.9) were asked to run for 45 minutes at submaximal intensity after melatonin-(6 mg) or placebo-ingestion, in a randomized and counterbalanced order. Heart rate (HR) and rectal temperature (Tre) evolution during exercise were measured. Blood samples were drawn twice (before and immediately after exercise) for the determination of triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-c), lactate, protein, and superoxide dismutase concentrations. The results showed that melatonin may disturb thermoregulatory control by exerting an effect on HR at 10 min of exercise, reducing HR by 6.6% (9 bpm; P < 0.001), and this effect decreased to 3.6% at the end of exercise (P < 0.01). Melatonin has no effect on triglycerides total cholesterol, HDL-c, lactate, and protein at rest and post-exercise. Although melatonin administration did not present a risk for cardiovascular function in healthy men, melatonin at high doses could decrease superoxide dismutase concentrations owing to the alteration of redox balance. These findings suggest that a high concentration of antioxidants does not enhance cardiovascular performance and may impair thermoregulatory control during prolonged exercise.

A biomimetic nanodrug self-assembled from small molecules for enhanced ferroptosis therapy

The ferroptosis drugs often induce oxidative damage or block antioxidant defense due to the key mechanism of ferroptosis in cancer treatment involved regulating the intracellular redox balance. However, these ferroptosis...

Antifungal Activity of N-(4-Halobenzyl)amides against Candida spp. and Molecular Modeling Studies

Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3–341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.

Physical Activity vs. Redox Balance in the Brain: Brain Health, Aging and Diseases

It has been proven that physical exercise improves cognitive function and memory, has an analgesic and antidepressant effect, and delays the aging of the brain and the development of diseases, including neurodegenerative disorders. There are even attempts to use physical activity in the treatment of mental diseases. The course of most diseases is strictly associated with oxidative stress, which can be prevented or alleviated with regular exercise. It has been proven that physical exercise helps to maintain the oxidant–antioxidant balance. In this review, we present the current knowledge on redox balance in the organism and the consequences of its disruption, while focusing mainly on the brain. Furthermore, we discuss the impact of physical activity on aging and brain diseases, and present current recommendations and directions for further research in this area.