Hyonok Yoon

ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis.

Resistance to the c‑Met inhibitor KRC‑108 induces the epithelial transition of gastric cancer cells

Investigation of the mechanisms of resistance to targeted therapies is essential as resistance acquired during treatment may lead to relapse or refractoriness to the therapy. Our previous study identified the small molecule KRC-108 as a result of efforts to find an anticancer agent with c-Met-inhibitory activity. In the present study, the changes accompanying resistance to KRC-108 were investigated in the gastric cancer cell line MKN-45 and its KRC-108-resistant clones by western blot and immunofluorescence analyses. Increased expression of the c-Met protein was observed in KRC-108-resistant cells compared with that of the parental cells, and the phosphorylation of c-Met also increased in cell lines resistant to KRC-108. Resistance to the c-Met inhibitor was associated with cell morphological changes: MKN-45 parental cells, which had a round and poorly differentiated morphology, were altered to exhibit an epithelial cell-like phenotype in KRC-108-resistant clones. Consistent with the transition to an epithelial morphology, the expression of E-cadherin was increased in resistant cells. Using immunoprecipitation, an interaction between E-cadherin and the c-Met protein was observed in the KRC-108-resistant cells. Immunohistochemical analysis of human gastric carcinoma tissues revealed the co-expression of E-cadherin and c-Met. These results suggest that the epithelial transition in KRC-108-resistant cells is mediated by recruiting E-cadherin to c-Met protein. Thus, the present study identified a mechanism used by cancer cells to confer resistance to anticancer agents.

Famciclovir as an antiviral agent for a patient with acute renal failure

Case Acyclovir is a widely administered medication for viral infection but is well known for its nephrotoxicity. To date, few studies regarding the safety of alternative antiviral agents have been reported. This study reports the case of a patient with renal dysfunction who suffers from acute herpes zoster (shingles) on her back. While renal function deteriorated with the use of acyclovir, the patient’s symptoms improved and baseline renal function recovered when she was treated with famciclovir. Conclusions Famciclovir could be taken as a first-line antiviral agent for patients with acute renal failure.

IMPLEMENTATION OF THE COMPLEX PROCESSING OF DYNAMIC PROGRAMMING WITH NONLINEAR TEMPLATES OF CELLULAR NEURAL NETWORKS

A complex processing of the dynamic programming is implemented with the parallel architecture of Cellular Neural Networks. Dynamic programming is an efficient algorithm to find optimal path and Cellular Neural Network is a parallel computation architecture composed of identical computation cell array and identical connections at each cell. Breaking down complex processing of the dynamic programming into a sequence of simple steps, the dynamic programming algorithm can be built with the nonlinear templates of Cellular Neural Networks. The procedure to breakdown the complex computation into the sequence of CNN building blocks is illustrated. To show the feasibility of the proposed method, the designed CNN-based dynamic programming is applied for detecting the traces of road boundaries. Edge information of road image is extracted and assigned as local distance value accordingly, then dynamic programming algorithm is implemented by a nonlinear CNN template. The proposed algorithm and its possible circuit structure are described, and simulation results are reported.