10/03/2024


DNA demethylases of the ten-eleven translocation (TET) family serve as tumor suppressors in various human cancers, but their pathogenic effects in coronary heart disease (CHD) remain unclear. Here we report that TET2 is transcriptionally upregulated in CHD patients, where it shows potential as a diagnostic tool. Mechanistic investigations revealed that TET2 facilitates inflammatory responses and cardiomyocyte apoptosis in rats through demethylation of microRNA-126 (miR-126) promoter. This interaction leads to sequestration of miR-126 from its target E2F transcription factor 3 (E2F3), contributing to E2F3 suppression in CHD. Upregulation of miR-126 when TET2 was silenced restored levels of inflammatory factors and aggravated the degree of cardiac injury and cardiomyocyte apoptosis in rats. By contrast, simultaneous overexpression of E2F3 and miR-126 reduced the levels of inflammatory factors, cardiac injury, and cardiomyocyte apoptosis in rats. Also, TET2 was found to regulate the activity of the PI3K-AKT pathway through the miR-126-E2F3 axis. Our findings uncover a novel function for TET2 in facilitating the progression of CHD.Background Breast cancer is one of the most prevalent cancers that often occur in females. Long noncoding RNA differentiation antagonizing nonprotein coding RNA (DANCR) has been involved in the pathogenesis of various tumors, including breast cancer. This study aimed to investigate the role and underlying mechanism of DANCR in breast cancer. https://www.selleckchem.com/products/LY2228820.html Materials and Methods The level of DANCR was detected in breast cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were estimated by the Transwell assay. The relationship between DANCR, miR-4319, and vesicle-associated membrane protein-associated protein B (VAPB) was confirmed by bioinformatic analysis and dual-luciferase reporter assay. The level of microRNA-4319 (miR-4319) was tested by qRT-PCR. The expression of VAPB was measured by qRT-PCR or western blot assay. Results DANCR and VAPB were upregulated, while miR-4319 was downregulated in breast cancer tissues and cells. Knockdown of DANCR hindered proliferation, migration, and invasion and promoted apoptosis of breast cancer cells. DANCR knockdown inhibited breast cancer development through regulating miR-4319. Inhibition of miR-4319 restrained breast cancer cell progression by targeting VAPB. Moreover, DANCR regulated VAPB expression by sponging miR-4319 in breast cancer cells. Conclusion DANCR facilitated breast cancer cell progression through regulating the miR-4319/VAPB axis, indicating that DANCR might be a potential biomarker and therapeutic target for breast cancer treatment.Background APOBEC1 complementation factor (A1CF) is a component of the apolipoprotein-B messenger RNA editing complex that participates in various cellular processes and acts as an oncogene in many cancers. In this study, it was aimed to investigate the roles of A1CF and its potential mechanism in endometrial cancer (EC). Materials and Methods Gene expression prolife was downloaded from The Cancer Genome Atlas database. Then Kaplan-Meier and Cox regression analyses were conducted to assess the prognostic value of A1CF in EC. Cell Counting Kit-8, plate clone formation, and transwell assays were used to estimate the functions of A1CF on the proliferation, invasion, and migration of EC cell. The gene set enrichment analysis was used to analyze the pathway that is enriched by A1CF, whereas quantitative real-time polymerase chain reaction and Western blot analyses were utilized to detect the mRNA and protein expression involved. Results It was detected that the upregulated A1CF was enriched in P53/P21 signaling pathway and tightly associated with patients' age, stage, and death. Besides, high A1CF expression led to a shorter overall survival of patients and predicted a poor prognosis in EC. The overexpression of A1CF promoted the proliferation, invasion, and migration of EC cells, whereas the depletion of A1CF suppressed these processes. Moreover, P21 and P53 were reduced whereas cyclin D1 and proliferating cell nuclear antigen were induced along with the increasing of A1CF. However, the effects of silencing A1CF on these protein expressions were on the contrary. Conclusion A1CF was highly expressed and closely related to the prognosis and progression of EC through the regulation of P53/P21 signaling pathway, providing a possible new therapy target site for EC.Organometallic complexes including metal carbonyls have been widely utilized in academic and industrial settings for purposes ranging from teaching basic catalytic reactions to developing state-of-the-art electronic circuits. Characterization of these materials can be obtained via steady-state measurements; however, the intermediate photochemical events remain unclear, hindering effective and rational molecular engineering methods for new materials. We employed femtosecond transient absorption (fs-TA) and ground-state femtosecond stimulated Raman spectroscopy (FSRS) on triphenylbismuth-tungsten pentacarbonyl complex, a solution precursor for bimetallic oxide thin films. Upon 280 nm excitation into a charge-transfer band, an ultrafast bimetallic bond dissociation occurs within ∼140 fs. The subpicosecond nondiffusive solvation events are followed by ∼10 ps (15 ps) methanol (ethanol) complexation of the nascent tungsten pentacarbonyl intermediate, which mainly undergoes vibrational relaxation after crossing into a hot ground state. The trans ligand to axial CO is revealed to play a key role in the electronic and vibrational structure and dynamics of the complex. These findings could power rational design of bimetallic and functional solution precursors for the light-driven nanopatterning of thin films.An enantioselective three-component reaction of diazoacetates, 2-oxo-3-ynoates, and nitrosoarenes has been developed by using a chiral N,N'-dioxide/Ni(OTf)2 complex. This catalytic manifold allows rapid access to a series of multifunctional chiral epoxides containing an imino ketone substituent in moderate to good yields (up to 82%) and excellent diastereo- and enantioselectivities (up to >95/5 dr and 99% ee) with high levels of Z/E ratios (up to >95/5 Z/E) under mild reaction conditions.