Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using β-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer.
Tetracycline (TC) antibiotics are one of the class of drugs widely used in clinical practice but also constitute a significant environmental concern. However, the adverse effects of TC on non-target organisms have not been well studied. The aim of this study was to examine the influence of exposure to high levels of TC on thalli of lichens to determine the impact on (1) physiological parameters including integrity of cell membranes, photosynthetic efficiency and viability, (2) oxidative stress response such as membrane lipid peroxidation, and (3) enzymatic antioxidant activities as catalase (CAT), superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR).
To evaluate the efficacy of human placental extract (HPE) eye drops compared to that of carboxymethylcellulose (CMC) and human peripheral blood serum (HPBS) eye drops in a mouse model of experimental dry eye (EDE) and corneal alkali burns. EDE and alkali burn models were induced in C57BL/6 mice using desiccating stress and NaOH, respectively. In both the EDE and alkali burn models, treatment groups received CMC, HPBS, or HPE eye drops.
Probiotics are microorganisms that provide health benefits at adequate doses and exhibit notable antioxidant and antimicrobial activities. These properties play crucial roles in combating chronic diseases linked to oxidative stress and antimicrobial resistance. This review aimed to summarize the antioxidant and antimicrobial properties of probiotics determined in in vitro studies and discuss mechanistic actions and analysis methods.
The central nervous system (CNS) comprises membranes and barriers that are vital to brain homeostasis. Membranes form a robust shield around neural structures, ensuring protection and structural integrity. At the same time, barriers selectively regulate the exchange of substances between blood and brain tissue, which is essential for maintaining homeostasis.
The research investigated the capacity of myo-inositol (MI) in order that it improves biochemical markers in serum and follicular fluid and, ultimately, intracytoplasmic sperm injection (ICSI) outcomes of women with PCOS. Sixty infertile patients with PCOS, who were undergoing ovulation induction for ICSI, were randomly divided to two groups. The MI group received 2000 mg myo-inositol + 1 mg folic acid twice a day for 6 weeks with starting the ICSI cycle.
