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t acute inhibition of stress-induced DNA methylation promotes rapid and sustained antidepressant effects associated with increased BDNF-TrkB-mTOR signaling in the PFC.Nod-like receptor protein 3 (NLRP3)-associated neuroinflammation mediated by activated microglia is involved in the pathogenesis of depression. The role of the pore-forming protein gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome mediating inflammatory programmed cell death, in depression has not been well defined. Here, we provide evidence that paeoniflorin (PF), a monoterpene glycoside compound derived from Paeonia lactiflora, ameliorated reserpine-induced mouse depression-like behaviors, characterized as increased mobility time in tail suspension test and forced swimming test, as well as the abnormal alteration of synaptic plasticity in the depressive hippocampus. The molecular docking simulation predicted that PF would interact with C-terminus of GSDMD. We further demonstrated that PF administration inhibited the enhanced expression of GSDMD which mainly distributed in microglia, along with the proteins involved in pyroptosis signaling transduction including gating depression given PF administration.Blooms of cyanobacteria cause enormous losses in both the economy and environment. Cyanophages are of great potential for fighting blooming cyanobacteria. Research report on cyanophage of bloom-forming cyanobacterium, Microcystis elabens is deficient. vB_MelS-Me-ZS1 (abbreviated as Me-ZS1) was isolated from fresh water by double-layer agar plate method using M. elabens. TEM exhibited that cyanosiphovirus Me-ZS1 has an icosahedral head about 60 nm in diameter, and a noncontractile tail approximately 260 nm. Experimental infection against 15 cyanobacterial strains showed that Me-ZS1 can infect 12 strains across taxonomic orders (Chroococcales, Nostocales and Oscillatoriales). High-throughput sequencing and bioinformatics analysis revealed that Me-ZS1 has a double-stranded DNA genome of 49,665 bp, with a G + C content of 58.22%, and 73 predicted open reading frames (ORFs). BLASTn and ORF comparisons showed that Me-ZS1 shares very low homology with the public sequences, and the phylogenetic tree based on TerL indicated that Me-ZS1 may delegate a novel and genetically distinct clade of Siphoviridae phages. In microcosm experiment, Me-ZS1 represented apparent effect on reducing relative abundance of cyanobacteria, increasing relative abundance of Saprospiraceae and protecting brocade carp (Carassius auratus) in cyanobacterial bloom water. This study isolated and characterized a novel broad-host-range Microcystis phage Me-ZS1 presenting a genetically distinct clade of freshwater cyanophage. The features of cyanophage Me-ZS1 provide a potential solution to the loss caused by cyanobacterial bloom.Cancer cells require higher levels of ATP for their sustained growth, proliferation, and chemoresistance. Mitochondrial matrix protein, C1qbp is upregulated in colon cancer cell lines. It protects the mitochondria from oxidative stress, by inhibiting the Membrane Permeability Transition (MPT) pore and providing uninterrupted synthesis of ATP. This intracellular interaction of C1qbp could be involved in chemoresistance development. Natural chemosensitizing agent, curcumin has been used in the treatment of multiple cancers. In this current study, we elucidate the role of C1qbp during curcumin induced chemosensitization to doxorubicin resistant colon cancer cells. The possible interaction between C1qbp and curcumin was determined using bioinformatics tools-AutoDock, SYBYL, and PyMol. #link# Intracellular doxorubicin accumulation by fluorimetry and dead cell count was carried out to determine development of chemoresistance. Effect of curcumin treatment and cytotoxicity was measured by MTT and lactate dehydrogenase release. Morphological analysis by phase contrast microscopy and colony forming ability by colonogenic assay were also performed. In addition, Cox-2 could mediate P-glycoprotein upregulation via phosphorylation of c-Jun. Thus, the gene level expression of P-glycoprotein and Cox-2 was also investigated using PCR. Through molecular docking we identified possible interaction between curcumin and C1qbp. G418 observed development of chemoresistance upon 6th day treatment. Concentration dependent alleviation of chemoresistance development by curcumin was confirmed and was found to reduce gene level expression of P-glycoprotein and Cox-2. Hence, curcumin could interact directly with C1qbp protein and this interaction could contribute to the chemosensiting effect to doxorubicin in colon cancer cells.Prolonged and excessive fluoride exposure can lead to fluorosis. The kidney is one of the organs that are injured mostly due to fluoride-induced damage. Fluoride can induce DNA damage at cytotoxic concentrations. This study aims to determine the extent of NaF-induced DNA damage and to investigate the effect of vitamin E and selenium combination (ES) in preventing and repairing this damage. For this purpose, we administered different combinations of NaF and ES to NRK-52E cells and determined the effective concentrations of ES and the NaF IC50 values associated with different incubation times (3, 12, and 24 h) by using the MTT assay. The determined quantities of NaF IC50 in association with time and the NaF IC50 + ES combination were administered to the cells. The extent of DNA damage was determined with the comet assay and the expression levels of the Ku70/80 and PARP-1 genes were determined with the RT-qPCR method. DNA damage significantly increased in all experimental groups compared to the control group (p less then 0.05). It was found out that the NaF and ES combination statistically reduced the DNA damage compared to the damage observed in the NaF-treated groups (p less then 0.05). Treatment of the ES combination significantly increased the expressions of Ku70 and Ku80 genes involved in DNA repair (p less then 0.05). We concluded that vitamin E and selenium can potentially be effective in the repair of fluoride-induced DNA damage based on the results of this in vitro study. Our results may shed light on the prevention of DNA damage associated with fluorosis.
Homepage: https://www.selleckchem.com/products/geneticin-g418-sulfate.html
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