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Background Cervical cancer, an aggressive gynecological cancer, seriously threatens women’s health worldwide. It is recently reported that neuropeptide substance P (SP) regulates many tumor-associated processes through neurokinin-1 receptor (NK1R). Therefore, we used cervical cancer cell line (HeLa) to investigate the functional relevance of the SP/NK1R system in cervical cancer pathogenesis. Methods Cellular proliferation and cytotoxicity were analyzed by colorimetric MTT assay. Quantitative real-time PCR (qRT-PCR) was used to measure mRNA expression levels of desired genes. Cell cycle distribution and apoptosis were evaluated by flow cytometry. A wound-healing assay was employed to assess migration ability. Results We found that the truncated isoform of NK1R(NK1R-Tr) is the dominantly expressed form of the receptor in Hela cells . We also indicated that that SP increased HeLa cell proliferation while treatment with NK1R antagonist, aprepitant, inhibited HeLa cell viability in a dose and time-dependent manner. SP also alters the levels of cell cycle regulators (up-regulation of cyclin B1 along with downregulation of p21) and apoptosis-related genes (up-regulation of Bcl-2 along with downregulation of Bax) while aprepitant reversed these effects. Aprepitant also induced arrest within the G2 phase of the cell cycle and subsequent apoptosis. Furthermore, SP promoted the migrative phenotype of HeLa cells and increased MMP-2 and MMP-9 expression while aprepitant exposure significantly reversed these effects. Conclusion Collectively, our results indicate the importance of the SP / NK1R system in promoting both proliferative and migrative phenotypes of cervical cancer cells and suggest that aprepitant may be developed as a novel treatment for combating cervical cancer.

The Lower Jurassic platform and basinal deposits exposed in the Montagna dei Fiori Anticline (Central Apennines, Italy) are pervasively affected by dolomitization. Based on the integration of field work, petrography, and geochemistry, two fault-related dolomitization events were recognized and interpreted as having occurred before and during the Apenninic orogeny. Fluid inclusion analysis indicates moderate to elevated salinity values of 3.5 to 20.5 and 12.8 to 18.6 eq. wt % NaCl in the first and the second event, respectively. The estimated salinities, in combination with δ18O values and 87Sr∕86Sr ratios, suggest significant involvement of evaporitic fluids in both events, most likely derived from the underlying Upper Triassic Burano Formation. In addition, the 87Sr∕86Sr ratios up to 0.70963 suggest the circulation of deep-sourced fluids that interacted with siliciclastic rocks and/or the crystalline basement during the dolomitization events. Two major dolomite types (D1 and D2) were recognized as pertaining to the first event, both postdated by high-amplitude bed-parallel stylolites, supporting a syn-burial pre-layer-parallel shortening dolomitization. A possible geodynamic framework for this dolomitization event is Early Jurassic to Late Jurassic rift-related extensional tectonism. The second dolomitization event (D3, D4, and D5) is characterized by a temperature upturn (up to 105 ∘C) and interpreted as associated with the inflow of hydrothermal fluids, possibly related to major changes in the permeability architecture of faults during early- to syn-thrusting and folding activity. Based on the timing of deformation in the Montagna dei Fiori Anticline, the second dolomitization event likely occurred in Late Miocene to Pliocene times. The findings regarding characteristics and timing of dolomitization here illustrates the long-term controlling role of the evaporitic detachments in the dolomitization process. This study shows that the Mg-rich fluids that were most likely derived from evaporites may prime the tectonically involved successions for repeated dolomitization, and hence the formation of potential reservoirs during sequential tectonic modifications (extensional vs. compressional).

This study aimed to evaluate chitosan (CS)-based formulations loaded with 5% sodium fluoride (NaF) and/or 10% nanohydroxyapatite (nHA) to remineralize the demineralized primary tooth enamel surface. Ninety enamel blocks were demineralized and were divided into six groups (n = 15): (1) CS-based hydrogel, (2) CS-based hydrogel loaded with NaF, (3) CS-based hydrogel loaded with nHA, (4) CS-based hydrogel loaded with NaF and nHA, (5) 5% NaF varnish, and (6) negative control with no intervention. After intervention, the specimens were pH cycled by 2 h immersion in demineralizing solution and 22 h immersion in remineralizing solution for 8 days. The remineralization effects were evaluated by Vickers microhardness measurements and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (FESEM-EDS). The best mean ± SD percentage microhardness recovery in remineralized enamel (%REMH) was found in group 4 (56.90 ± 5.49). The %REMH of groups 2 (30.74 ± 3.51) and 5 (29.23 ± 5.65) were statistically the same (p = 0.943). FESEM images confirmed partial coverage of the porous demineralized enamel with a newly formed mineralized layer. Based on EDS findings, the Ca/P ratio values of the treated enamel surfaces with CS-based hydrogels ranged between 1.71 and 1.87, and the highest F content was noticed in group 2 (1.02 ± 0.03). Although, all tested CS-based hydrogels demonstrated the potential to repair demineralized enamel, nHA- and NaF-containing CS-based hydrogel showed the highest remineralization effect. We infer that this new hybrid hydrogel is a potentially useful dental material for tooth biomineralization.