Pyridine appended pyrimidine bis hydrazone: Zn2+/ATP detection, bioimaging and functional properties of its dinuclear Zn(II) complex.

A pyridine functionalized pyrimidine-based system, H2P was successfully synthesized, characterized, and evaluated for its remarkable selective characteristics towards Zn2+ and ATP ions. The chemical sensing capabilities of H2P were demonstrated through absorption, fluorescence, and NMR spectroscopic techniques. The probe exhibited outstanding sensitivity when interacting with the ions, demonstrating relatively strong association constants and impressively low detection limits. The comprehensive binding mechanism of H2P with respect to Zn2+ and ATP ions was investigated using a combination of analytical methods, including Job's plot, NMR spectroscopy, mass spectrometry, and density functional theory (DFT) experiments. The interesting sensing ability of H2P for Zn2+/ATP ions was harnessed for live cell bioimaging and other diverse on-site detection purposes, including paper strips, cotton swabs, and applications involving mung bean sprouts. Further, the fluorescent probe demonstrated its effectiveness in detecting Zn2+ and ATP within live cells, indicating its significant potential in the realm of biological imaging applications. Moreover, the molecular configuration of the zinc complex (H2P-Zn2Cl4), derived from H2P, was elucidated using X-ray crystallography. This complex exhibited intriguing multifunctional attributes, encompassing its capability for detecting picric acid and for reversible acid/base sensing responses. The enhanced conducting behavior of the complex as well as its resistance properties were investigated by performing I-V characteristics and electrochemical impedance spectroscopic (EIS) experiments respectively.

Restoration of functional PAX3 transcriptional factor enhanced neuronal differentiation in PAX3b isoform-depleted neuroblastoma cells.

Reexpressed PAX3 transcription factor is believed to be responsible for the differentiation defects observed in neuroblastoma. Although the importance of PAX3 in neuronal differentiation is documented how it is involved in the defective differentiation remains unexplored particularly with its isoforms. Here, first we have analyzed PAX3 expression, its functional status, and its correlation with the neuronal marker expression in SH-SY5Y and its parental SK-N-SH cells. We have found that SH-SY5Y cells which expressed more PAX3 showed increased expression of neuronal marker genes (TUBB, MAP2, NEFL, NEUROG2, SYP) and reported PAX3 target genes (MET, TGFA, and NCAM1) than the SK-N-SH cells that had low PAX3 level. Retinoic acid treatment is unable to induce neuronal differentiation in cells (SK-N-SH) with low PAX3 level/activity. Moreover, ectopic expression of PAX3 in SK-N-SH cells neither induces neuronal marker genes nor its target genes. PAX3 isoform expression analysis revealed the expression of PAX3b isoform that contains only paired domain in SK-N-SH cells, whereas in SH-SY5Y cells, we could also observe PAX3c isoform that contains all functional domains. Further, PAX3b depletion in SK-N-SH cells is not induced PAX3 target genes, and the cells remain poorly differentiated. Interestingly, ectopic PAX3 expression in PAX3b-depleted SK-N-SH cells enhanced neuronal outgrowth along with neuronal marker gene induction. Collectively, these results showed that the PAX3b isoform may be responsible for the differentiation defect observed in SK-N-SH cells and restoration of functional PAX3 in the absence of PAX3b can induce neurogenesis in these cells.