Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression.

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.

Expected Value of Multiplicative Degree-Kirchhoff Index in Random Polygonal Chains.

The multiplicative degree-Kirchhoff index is a significant topological index. This paper is devoted to the exact formulas for the expected value of the multiplicative degree-Kirchhoff index in random polygonal chains. Moreover, on the basis of the result above, the multiplicative degree-Kirchhoff index of all polygonal chains with extremal values and average values are obtained.

Coupling of the Surface and Near-Bottom Currents in the Gulf of Mexico.

Coupling between the surface and near-bottom currents in the Gulf of Mexico (GoM) has been reported in many case studies. However, geographical variations of this coupling need more examination. In this study, surface geostrophic currents derived from satellite-observed sea surface height and subsurface currents from a collection of deep ocean moorings are used to examine the surface and bottom coupling in different parts of the GoM. The short-period (30-90 days) fluctuations generated by the Loop Current (LC) and the LC eddies (LCEs) have a more vertically coherent structure and stronger deep ocean expressions than the long-period fluctuations (>90 days). In addition, the strength of the coupling is modulated by the long-period variations of the LC and LCE sheddings. Moreover, the surface and bottom coupling varies geographically. In the LC region, the surface fluctuations along the eastern side of the LC are important in causing the bottom current fluctuations through baroclinic instability under the LC and through traveling topographic Rossby waves (TRWs) north of the LC. In the central deep GoM, the bottom currents are affected by the upper fluctuations of the northern LC through both local baroclinic instability and remote TRW propagation. In the northwestern GoM, the bottom current fluctuations are largely related to the remote surface variability from the west side of the LC by TRWs propagating northwestward. This study will help us better understand mechanisms of the bottom current fluctuations that are important for the dispersal of deep ocean materials and properties.

Vertical redistribution of salt and layered changes in global ocean salinity.

Salinity is an essential proxy for estimating the global net freshwater input into the ocean. Due to the limited spatial and temporal coverage of the existing salinity measurements, previous studies of global salinity changes focused mostly on the surface and upper oceans. Here, we examine global ocean salinity changes and ocean vertical salt fluxes over the full depth in a dynamically consistent and data-constrained ocean state estimate. The changes of the horizontally averaged salinity display a vertically layered structure, consistent with the profiles of the ocean vertical salt fluxes. For salinity changes in the relatively well-observed upper ocean, the contribution of vertical exchange of salt can be on the same order of the net surface freshwater input. The vertical redistribution of salt thus should be considered in inferring changes in global ocean salinity and the hydrological cycle from the surface and upper ocean measurements.

Surface-generated mesoscale eddies transport deep-sea products from hydrothermal vents.

Atmospheric forcing, which is known to have a strong influence on surface ocean dynamics and production, is typically not considered in studies of the deep sea. Our observations and models demonstrate an unexpected influence of surface-generated mesoscale eddies in the transport of hydrothermal vent efflux and of vent larvae away from the northern East Pacific Rise. Transport by these deep-reaching eddies provides a mechanism for spreading the hydrothermal chemical and heat flux into the deep-ocean interior and for dispersing propagules hundreds of kilometers between isolated and ephemeral communities. Because the eddies interacting with the East Pacific Rise are formed seasonally and are sensitive to phenomena such as El Niño, they have the potential to introduce seasonal to interannual atmospheric variations into the deep sea.