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While both materials provide similar success rates, the shorter treatment time with MTA may translate into higher overall success rates because of better patient compliance.

Inhibitory GABA-ergic neurotransmission is fundamental for the adult vertebrate central nervous system and requires low chloride concentration in neurons, maintained by KCC2, a neuroprotective ion transporter that extrudes intracellular neuronal chloride. To identify Kcc2 gene expression‑enhancing compounds, we screened 1057 cell growth-regulating compounds in cultured primary cortical neurons. We identified kenpaullone (KP), which enhanced Kcc2/KCC2 expression and function in cultured rodent and human neurons by inhibiting GSK3ß. KP effectively reduced pathologic pain-like behavior in mouse models of nerve injury and bone cancer. In a nerve-injury pain model, KP restored Kcc2 expression and GABA-evoked chloride reversal potential in the spinal cord dorsal horn. Delta-catenin, a phosphorylation-target of GSK3ß in neurons, activated the Kcc2 promoter via KAISO transcription factor. Transient spinal over-expression of delta-catenin mimicked KP analgesia. Our findings of a newly repurposed compound and a novel, genetically-encoded mechanism that each enhance Kcc2 gene expression enable us to re-normalize disrupted inhibitory neurotransmission through genetic re-programming.

Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell-death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit-8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP). Finally, the expression levels of numerous mitochondrial-associated apoptosis proteins were assessed by western blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3. GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat cells; however, this effect was ameliorated by subsequent treatment with mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent than GRg3 in inhibiting cell proliferation and reducing MMP. In addition, expression levels of apoptosis-associated proteins were significantly increased in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia.

Bacteria are the primary food source of choanoflagellates, the closest known relatives of animals. Studying signaling interactions between the Gram-negative Bacteroidetes bacterium Algoriphagus sp. PR1 and its predator, the choanoflagellate Salpingoeca rosetta, provides a promising avenue for testing hypotheses regarding the involvement of bacteria in animal evolution. Here we announce the complete genome sequence of Algoriphagus sp. PR1 and initial findings from its annotation.

BackgroundHuman aging is a hot topic in biology, and it has been associated with DNA methylation changes at specific genomic sites. We aimed to study the changes of DNA methylation at a single-CpG-site resolution using peripheral blood samples from centenarians.MethodsUsing Illumina 450 K Methylation BeadChip microarray assays, we carried out a pool-based, epigenome-wide investigation of DNA methylation of blood samples from 12 centenarians and 12 healthy controls. Differentially methylated cytosine-phosphate-guanosine (CpG) sites were selected for further pyrosequencing analysis of blood samples from 30 centenarians and 30 healthy controls.ResultWe identified a total of 31 high-confidence CpG sites with differential methylation profiles between the groups: 9 (29%) were hypermethylated and 22 (71%) were hypomethylated in centenarians. It was also found that hypermethylation of HKR1 and hypomethylation of ROD1 and NLRC5 genes strongly correlated with age in centenarians.ConclusionOur results indicate that the methylation profile combination of HKR1, ROD1, and NLRC5 could be a promising biomarker for aging in Hainan centenarians.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0334-1) contains supplementary material, which is available to authorized users.

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