Combinational Inhibition of MEK and AKT Synergistically Induces Melanoma Stem Cell Apoptosis and Blocks NRAS Tumor Growth.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MICs), implicated in tumorigenesis, invasion, and drug resistance, and characterized by an elevated expression of stem cell markers, including CD133. siRNA knockdown of CD133 has been previously shown to enhance apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133's anti-apoptotic activity in patient-derived BAKP melanoma, harboring the difficult-to-treat NRAS driver mutation, after CRISPR-Cas9 CD133 knockout or Doxycycline (Dox)-inducible re-expression of CD133.

Temperature Is a Key Factor Governing the Toxic Impact of Ultra-Violet Radiation-Emitting Nail Dryers When Used on Human Skin Cells.

The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging.

Automated Method for Intracranial Aneurysm Classification Using Deep Learning.

Intracranial aneurysm (IA) is now a common term closely associated with subarachnoid hemorrhage. IA is the bulging of a blood vessel caused by a weakening of its wall. This bulge can rupture and, in most cases, cause internal bleeding.

CD133 Stimulates Cell Proliferation via the Upregulation of Amphiregulin in Melanoma.

CD133, a cancer stem cell (CSC) marker in tumors, including melanoma, is associated with tumor recurrence, chemoresistance, and metastasis. Patient-derived melanoma cell lines were transduced with a Tet-on vector expressing CD133, generating doxycycline (Dox)-inducible cell lines. Cells were exposed to Dox for 24 h to induce CD133 expression, followed by RNA-seq and bioinformatic analyses, revealing genes and pathways that are significantly up- or downregulated by CD133.

TRIP12 governs DNA Polymerase β involvement in DNA damage response and repair.

The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, present a challenge for genome integrity maintenance as this requires the engagement of different DNA repair pathways. Specific 'repair controllers' that facilitate DNA repair pathway crosstalk between double strand break (DSB) repair and base excision repair (BER), and regulate BER protein trafficking at lesion sites, have yet to be identified. We find that DNA polymerase β (Polβ), crucial for BER, is ubiquitylated in a BER complex-dependent manner by TRIP12, an E3 ligase that partners with UBR5 and restrains DSB repair signaling.