Biology subjects

Russo, G. L.

Publications and source records attributed to Russo, G. L..

3 recordsLinked to original sources

bioRxiv2024

The chemopreventive effects of Curcumin against oxidative stress induced by Cadmium or H2O2 are mediated by Nrf2/ARE signaling and protective autophagy in myeloid cells

The evidence linking high levels of environmental pollutants to chronic degenerative diseases is alarming, with heavy metals (HM) identified as a key factor. Research suggests that certain phytochemicals in the diet can reduce HM levels and mitigate their adverse health effects.Curcumin (Cur), a natural polyphenol, is particularly effective in protecting against Cadmium (Cd) toxicity. The present study demonstrates that preincubation with low doses of Cur (1 M) in differentiated HL-60 and K-562 human myeloid cells can significantly protect against cytotoxicity induced by Cd and or H2O2. Cur reduced the increased levels of reactive oxygen species (ROS) generated by Cd or H2O2 by inducing a protective form of autophagy. Cur activated mild oxidative stress that triggers the expression of Nrf2-dependent transcripts, such as HO and NQO1. The potential chemopreventive effects of Cur against redox stress have been strengthened by the observation that free and unmetabolized Cur is detectable inside the cells after 5 minutes of treatment, and its presence parallels with increased levels of intracellular GSH. These findings suggest that supplementation with Cur in the form of nutraceuticals may represent a promising way to protect people living in highly polluted areas against the adverse effects of HM contaminants.

cell biology↗

bioRxiv2023

An organic extract from ascidian Ciona robusta induces cytotoxic autophagy in human malignant cell lines

The last decades have seen an increase in the isolation and characterization of anticancer compounds derived from marine organisms, especially invertebrates, and their use in clinical trials. In this regard, ascidians, which are included in the subphylum Tunicata, represent successful examples with two drugs, Aplidine(C) and Yondelis(C), that reached the market as orphan drugs against several malignancies. Here, we report that an organic extract prepared from homogenized tissues of the Mediterranean ascidian Ciona robusta inhibited cell proliferation in HT-29, Hep G2, and U2 OS human cells with the former resulting as the most sensitive to the extract (EC50 = 250 {micro}g/ml). We demonstrated that the ascidian organic extract was not cytotoxic on HT-29 cells induced to differentiate with sodium butyrate, suggesting a preference for the mixture for the malignant phenotype. Finally, we reported that the cell death induced by the organic extract was mediated by the activation of a process of cytotoxic autophagy as a result of the increased expression of the LC3-II marker and the number of autophagic vacuoles, which almost doubled in treated HT-29 cells. In summary, although the detailed chemical composition of the Ciona robusta extract is still undetermined, our data suggest the presence in it of bioactive compounds possessing anticancer activity.

pharmacology and toxicology↗

bioRxiv2021

Optical activation of TrkB neurotrophin receptor in mouse ventral hippocampus promotes plasticity and facilitates fear extinction

Successful extinction of traumatic memories depends on neuronal plasticity in the fear extinction network. However, the mechanisms involved in the extinction process remain poorly understood. Here, we investigated the fear extinction network by using a new optogenetic technique that allows temporal and spatial control of neuronal plasticity in vivo. We optimized an optically inducible TrkB (CKII-optoTrkB), the receptor of the brain-derived neurotrophic factor, which can be activated upon blue light exposure to increase plasticity specifically in pyramidal neurons. The activation of CKII-optoTrkB facilitated the induction of LTP in Schaffer collateral-CA1 synapses after brief theta-burst stimulation and increased the expression of FosB in the pyramidal neurons of the ventral hippocampus, indicating enhanced plasticity in that brain area. We showed that optical stimulation of the CA1 region of the ventral hippocampus during fear extinction training led to an attenuated conditioned fear memory. This was a specific effect only observed when combining extinction training with CKII-optoTrkB activation, and not when using either intervention alone. Thus, TrkB activation in ventral CA1 pyramidal neurons promotes a state of neuronal plasticity that allows extinction training to guide neuronal network remodeling to overcome fear memories. Our methodology is a powerful tool to induce neuronal network remodeling in the adult brain, and can attenuate neuropsychiatric symptoms caused by malfunctioning networks.

neuroscience↗