Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Jan 2018
Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux.
Blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen-glucose deprivation. ⋯ LiCl significantly induced the extent of autophagic flux after SCI by increasing LC3-II and ATG-5 levels, and abolishing p62 accumulation. In addition, a combination of LiCl and the autophagy inhibitor chloroquine not only partially eliminated the BSCB-protective effect of LiCl, but also exacerbated TJ protein degradation both in vivo and in vitro. Together, these findings suggest that LiCl treatment alleviates BSCB disruption and promotes locomotor recovery after SCI, partly by stimulating autophagic flux.
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Biochem. Biophys. Res. Commun. · Jan 2019
The immunotherapeutic effects of recombinant Bacillus Calmette-Guérin resistant to antimicrobial peptides on bladder cancer cells.
Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure and unwanted side effects. Here, we generated genetically modified BCG strains with improved immunotherapeutic effects by adding genes that confer evasion of AMPs. ⋯ rBCG-Sic and rBCG-dltA can effectively evade BCG-stimulated AMPs, and may be significantly improved immunotherapeutic tools to treat bladder cancer.
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Biochem. Biophys. Res. Commun. · May 2017
Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the Mycobacterium tuberculosis repressor EthR2.
Inhibition of transcriptional regulators of bacterial pathogens with the aim of reprogramming their metabolism to modify their antibiotic susceptibility constitutes a promising therapeutic strategy. One example is the bio-activation of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by inhibiting the transcriptional repressor EthR. ⋯ The x-ray structure of EthR2 was solved at 2.3 Å resolution in complex with a compound called SMARt-420 (Small Molecule Aborting Resistance). Detailed comparison and structural analysis revealed interesting insights for the upcoming structure-based design of EthR2 inhibitors as an alternative to revert ethionamide resistance in Mycobacterium tuberculosis.
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Biochem. Biophys. Res. Commun. · Apr 2019
Circular RNA hsa_circ_0001368 suppresses the progression of gastric cancer by regulating miR-6506-5p/FOXO3 axis.
Gastric cancer (GC) is still a major aggressive malignancy worldwide. While the importance of circular RNAs (circRNAs) involved in carcinogenesis has gradually been acknowledged, their role in human cancers is not largely understood, including in GC. Here, we focused on hsa_circ_0001368 in GC, a novel circRNA that has not been previously reported. ⋯ Mechanically, we demonstrated that hsa_circ_0001368 served as a competing endogenous RNA (ceRNA) to sponge miR-6506-5p. Subsequently, FOXO3 may act as the functional target of miR-6506-5p, and the knockdown of hsa_circ_0001368 decreased the expression of the tumor-suppressive gene FOXO3. Taken together, our study revealed that hsa_circ_0001368 plays a tumor-suppression role in GC via the miR-6506-5p/FOXO3 axis and may serve as a potential target for GC therapy.
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Biochem. Biophys. Res. Commun. · Feb 2019
The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss.
Oxidative damage plays a critical role in cochlear cell apoptosis, which is central to the physiopathology of noise-induced hearing loss (NIHL). Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase that regulates cellular response to oxidative stress, however, its role in NIHL remains poorly understood. Here, we report that SIRT2 is upregulated in the cochlea after noise exposure. ⋯ Moreover, AK-7 treatment reduces apoptosis of mouse inner ear HEI-OC1 cells exposed to oxidative stress in vitro. Taken together, these results suggest that SIRT2 inhibition with AK-7 reduces cochlear cell apoptosis through attenuating oxidative stress-induced damage, which may underlie its protective role against NIHL. This study also implies that AK-7 may have potential therapeutic significance in the intervention of NIHL.