MicroRNA-329-mediated PTTG1 downregulation inactivates the MAPK signaling pathway to suppress cell proliferation and tumor growth in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a severe malignancy usually producing a poor prognosis and high mortality rate. MicroRNAs (miRNAs) have been reported in association with CCA; however, the role miR-329 plays in the CCA condition still remains unclear. Therefore, this study was conducted to explore the underlying mechanism of which miR-329 is influencing the progression of CCA. This work studied the differential analysis of the expression chips of CCA obtained from the Gene Expression Omnibus database. Next, to determine both the expression and role of pituitary tumor transforming gene-1 (PTTG1) in CCA, the miRNAs regulating PTTG1 were predicted. In the CCA cells that had been intervened with miR-329 upregulation or inhibition, along with PTTG1 silencing, expression of miR-329, PTTG1, p-p38/p38, p-ERK5/ERK5, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bcl-2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2), and caspase-3 were determined. The effects of both miR-329 and PTTG1 on cell proliferation, cell-cycle distribution, and apoptosis were also assayed. The miR-329 was likely to affect the CCA development through regulation of the PTTG1-mediated mitogen-activated protein kinase (MAPK) signaling pathway. The miR-329 targeted PTTG1, leading to inactivation of the MAPK signaling pathway. Upregulation of miR-329 and silencing of PTTG1 inhibited the CCA cell proliferation, induced cell-cycle arrest, and subsequently promoted apoptosis with elevations in Bax, cleaved caspase-3, and total caspase-3, but showed declines in PCNA, Cyclin D1, and Bcl-2. Moreover, miR-329 was also found to suppress the tumor growth by downregulation of PTTG1. To summarize, miR-329 inhibited the expression of PTTG1 to inactivate the MAPK signaling pathway, thus suppressing the CCA progression, thereby providing a therapeutic basis for the CCA treatment.

Efficient removal of Cd2+ and Pb2+ from aqueous solution with amino- and thiol-functionalized activated carbon: Isotherm and kinetics modeling.

In order to address the increasingly severe pollution issue caused by heavy metals, activated carbon-based absorbents have gained considerable attention. Herein, two novel adsorbents, amino-functionalized activated carbon (N-AC) and thiol-functionalized activated carbon (S-AC), were successfully synthesized by stepwise modification with tetraethylenepentamine (TEPA), cyanuric chloride (CC) and sodium sulfide. The pristine and synthesized materials were characterized by BET analysis, SEM, FTIR spectroscopy, elemental analysis and zeta-potential analyzer. Meanwhile, their adsorption properties for Cd2+ and Pb2+ and the effects of various variables on the adsorption processes were systematically investigated. The findings confirmed that amino-groups and thiol-groups endowed the AC with a strong affinity for metal ions and that the pH of solution affected the uptake efficiencies of the adsorbents by influencing their surface charges. Furthermore, six isotherm models (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Sips and Redlich-Peterson) and four kinetic models (pseudo-first-order, pseudo-second-order, Intra-particle diffusion and Elovich) were applied to interpret the adsorption process at three different temperatures (288 K, 298 K and 308 K). The results indicated that temperature played an important role and that the rate-limiting step was chemosorption. A better fit for all adsorption systems was obtained with Langmuir model, with the maximum adsorption capacities at 298 K of 79.20 mg Cd2+/g and 142.03 mg Pb2+/g for N-AC, 130.05 mg Cd2+/g and 232.02 mg Pb2+/g for S-AC, respectively. Subsequently, the thermodynamic parameters revealed the nature of the adsorption was endothermic and spontaneous under the experimental condition. The possible adsorption procedures and the underlying mechanisms comprising physical and chemical interactions were proposed. Moreover, the as-synthesized adsorbents exhibited excellent regeneration performance after five adsorption/desorption cycles. The overall results demonstrated that both N-AC and S-AC could be the promising efficient candidates for removing Cd2+ and Pb2+ from contaminated water.