Adult brains have limited regenerative capacity. Consequently, both brain damage and neurodegenerative diseases often cause functional impairment for patients. Mesenchymal stem cells (MSCs), one type of adult stem cells, can be isolated from various adult tissues. MSCs have been used in clinical trials to treat human diseases and the therapeutic potentials of the MSC‐derived secretome and extracellular vesicles (EVs) have been under investigation. We found that blocking the prostaglandin E 2 /prostaglandin E 2 receptor 4 (PGE 2 /EP 4 ) signaling pathway in MSCs with EP 4 antagonists increased EV release and promoted the sorting of specific proteins, including anti‐inflammatory cytokines and factors that modify astrocyte function, blood–brain barrier integrity, and microglial migration into the damaged hippocampus, into the EVs. Systemic administration of EP 4 antagonist‐elicited MSC EVs repaired deficiencies of cognition, learning and memory, inhibited reactive astrogliosis, attenuated extensive inflammation, reduced microglial infiltration into the damaged hippocampus, and increased blood–brain barrier integrity when administered to mice following hippocampal damage. stem cells translational medicine 2019

Cadmium is a known environmental carcinogen. Exposure of Cd leads to the activation of several proto-oncogenes in cells. We investigated here the mechanism of c-Myc expression in hepatic cells under Cd treatment. The c-Myc protein and mRNA levels increased in dose- and time-dependent manners in HepG2 cells with Cd treatment. This increase was due to an increase in c-Myc mRNA stability. To explore the mechanism involved in enhancing the mRNA stability, several cellular signaling factors that evoked by Cd treatment were analyzed. PI3K, p38, ERK and JNK were activated by Cd. However, ERK did not participate in the Cd-induced c-Myc expression. Further analysis revealed that mTORC2 was a downstream factor of p38. PI3K, JNK and mTORC2 coordinately activated Akt. Akt was phosphorylated at Thr450 in the untreated cells. Cd treatment led to additional phosphorylation at Thr308 and Ser473. Blocking any of the three signaling factors resulted in the reduction of phosphorylation level at all three Akt sites. The activated Akt phosphorylated Foxo1 and allowed the modified protein to translocate into the cytoplasm. We conclude that Cd-induced accumulation of c-Myc requires the activation of several signaling pathways. The signals act coordinately for Akt activation and drive the Foxo1 from the nucleus to the cytoplasm. Reduction of Foxo1 in the nucleus reduces the transcription of its target genes that may affect c-Myc mRNA stability, resulting in a higher accumulation of the c-Myc proteins.

In this paper, we propose a switching bilateral filter (SBF) with a texture and noise detector for universal noise removal. Operation was carried out in two stages: detection followed by filtering. For detection, we propose the sorted quadrant median vector (SQMV) scheme, which includes important features such as edge or texture information. This information is utilized to allocate a reference median from SQMV, which is in turn compared with a current pixel to classify it as impulse noise, Gaussian noise, or noise-free. The SBF removes both Gaussian and impulse noise without adding another weighting function. The range filter inside the bilateral filter switches between the Gaussian and impulse modes depending upon the noise classification result. Simulation results show that our noise detector has a high noise detection rate as well as a high classification rate for salt-and-pepper, uniform impulse noise and mixed impulse noise. Unlike most other impulse noise filters, the proposed SBF achieves high peak signal-to-noise ratio and great image quality by efficiently removing both types of mixed noise, salt-and-pepper with uniform noise and salt-and-pepper with Gaussian noise. In addition, the computational complexity of SBF is significantly less than that of other mixed noise filters.

Arsenic and its compounds are toxic environmental pollutants and known carcinogens.