ZBTB34 is a hepatocellular carcinoma-associated protein with a monopartite nuclear localization signal.

ZBTB34 is a novel zinc finger protein with an unknown function. In this study, the gene expression and survival prognosis of ZBTB34 were analyzed across tumors based on the TCGA datasets. According to the bioinformatics analysis and qPCR results, liver hepatocellular carcinomas exhibit a high level of ZBTB34 expression. Additionally, the experiment supported the bioinformatics analysis findings that ZBTB34 expression was regulated by miR-125b-5p and that ZBTB34 affected ZBTB10, POLR1B, and AUH expression in HepG2 cells. Biological software analysis further revealed that ZBTB34 contains a monopartite nuclear localization signal (NLS). Arginine and lysine inside the putative NLS were substituted using the alanine-scanning mutagenesis method. The findings showed that the ability of ZBTB34 to enter the nucleus was abolished by the alanine substitution of the sequence 320RGGRARQKRA329 and the mutation of Lys327 and Arg328 residues. ZBTB34 was co-immunoprecipitated with importin α1, importin α3, importin α4, and importin ß1, according to the results of the co-immunoprecipitation assay. In conclusion, ZBTB34 is a hepatocellular carcinoma-associated protein with a monopartite NLS. The nuclear import of ZBTB34 is mediated by importin α1, importin α3, importin α4, and importin ß1. ZBTB34 performs its biological functions via a putative miR-125b-5p/ZBTB34/(ZBTB10, POLR1B, and AUH) signaling axis in HepG2 cells.

Zbtb34 promotes embryonic stem cell proliferation by elongating telomere length.

Zbtb34 is a novel zinc finger protein, which is revealed by biological software analysis to have 3 zinc fingers, but its functions remain unknown. In this study, mouse Zbtb34 cDNA was amplified by PCR and inserted into the plasmid pEGFP-N1 to generate Zbtb34-EGFP fusion protein. The upregulation of Zbtb34 in mouse embryonic stem cells promoted telomere elongation and increased cell proliferation. In order to understand the above phenomena, the telomere co-immunoprecipitation technique was employed to investigate the relationship between Zbtb34 and telomeres. The results indicated that Zbtb34 could bind to the DNA sequences of the telomeres. Alanine substitution of the third zinc finger abolished such binding. Since Pot1 is the only protein binding to the single-stranded DNA at the end of the telomeres, we further investigated the relationship between Zbtb34 and Pot1. The results revealed that the upregulation of Zbtb34 decreased the binding of Pot1b to the telomeres. Through the upregulation of Pot1b, the binding of Zbtb34 to the telomeres was also reduced. In conclusion, we showed that the main biological function of Zbtb34 was to bind telomere DNA via its third ZnF, competing with Pot1b for the binding sites, resulting in telomere elongation and cell proliferation.

The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.

Epigenetics in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease with unknown pathogenesis and complex pathological manifestations. At present, a large number of studies on targeted drugs for the typical pathological phenomenon of AD (Aß) have ended in failure. Although there are some drugs on the market that indirectly act on AD, their efficacy is very low and the side effects are substantial, so there is an urgent need to develop a new strategy for the treatment of AD. An increasing number of studies have confirmed epigenetic changes in AD. Although it is not clear whether these epigenetic changes are the cause or result of AD, they provide a new avenue of treatment for medical researchers worldwide. This article summarizes various epigenetic changes in AD, including DNA methylation, histone modification and miRNA, and concludes that epigenetics has great potential as a new target for the treatment of AD.