IRE1α Inhibitors as a Promising Therapeutic Strategy in Blood Malignancies.

Synthesis, folding, and structural maturation of proteins occur in the endoplasmic reticulum (ER). Accumulation of misfolded or unfolded proteins in the ER lumen contributes to the induction of ER stress and activation of the unfolded protein response (UPR) signaling pathway. Under ER stress, the UPR tries to maintain cellular homeostasis through different pathways, including the inositol-requiring enzyme 1 alpha (IRE1α)-dependent ones.

Temporomandibular Disorders, Bruxism, Perceived Stress, and Coping Strategies among Medical University Students in Times of Social Isolation during Outbreak of COVID-19 Pandemic.

The COVID-19 pandemic caught universities along with their students off-guard, enforcing online education. Fear of the unknown, disinformation, and isolation resulted in an increased stress level in the entire population. Medical university students are particularly endangered with high stress levels and developing TMD.

The Toxicity of Universal Dental Adhesives: An In Vitro Study.

There is no consensus in the literature regarding the potential toxicity of universal dental adhesives (UDA). Being used in close proximity to the pulp, their biocompatibility should be an important factor in dental research. The aim of the present study was to evaluate the biocompatibility of UDA in an in vitro model.

The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate.

Inositol-requiring enzyme type 1 (IRE1) is a serine/threonine kinase acting as one of three branches of the Unfolded Protein Response (UPR) signaling pathway, which is activated upon endoplasmic reticulum (ER) stress conditions. It is known to be capable of inducing both pro-survival and pro-apoptotic cellular responses, which are strictly related to numerous human pathologies. Among others, IRE1 activity has been confirmed to be increased in cancer, neurodegeneration, inflammatory and metabolic disorders, which are associated with an accumulation of misfolded proteins within ER lumen and the resulting ER stress conditions.

The Cytotoxicity and Genotoxicity of Three Dental Universal Adhesives-An In Vitro Study.

Dental universal adhesives are considered an useful tool in modern dentistry as they can be used in different etching techniques, allow for simplified protocol and provide sufficient bond strength. However, there is still no consensus as to their toxicity towards pulp. Thus, the present study aimed to evaluate the cytotoxicity and genotoxicity of three universal adhesives: OptiBond Universal, Prime&Bond Universal and Adhese in an in vitro experimental model, monocyte/macrophage cell line SC (ATCC CRL-9855).

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases.

Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism-accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner.

Use of Small-molecule Inhibitory Compound of PERK-dependent Signaling Pathway as a Promising Target-based Therapy for Colorectal Cancer.

Background: Colorectal cancer constitutes one of the most common cancer with a high mortality rate. The newest data has reported that activation of the pro-apoptotic PERK-dependent unfolded protein response signaling pathway by small-molecule inhibitors may constitute an innovative anti-cancer treatment strategy.

Objective: In the presented study, we evaluated the effectiveness of the PERK-dependent unfolded protein response signaling pathway small-molecule inhibitor 42215 both on HT-29 human colon adenocarcinoma and CCD 841 CoN normal human colon epithelial cell lines.

Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis.

Cancer constitutes a grave problem nowadays in view of the fact that it has become one of the main causes of death worldwide. Poor clinical prognosis is presumably due to cancer cells metabolism as tumor microenvironment is affected by oxidative stress. This event triggers adequate cellular response and thereby creates appropriate conditions for further cancer progression.

Inhibition of the PERK-Dependent Unfolded Protein Response Signaling Pathway Involved in the Pathogenesis of Alzheimer's Disease.

Objectives: There is a body of evidence that neurodegenerative disease entities are directly correlated with the perturbations on the molecular level. Hence, the ER stress-mediated Unfolded Protein Response (UPR) is activated resulting in PERK-dependent phosphorylation of the Eukaryotic initiation factor 2 (eIF2α). Thus, the levels of ATF4 and CHOP proteins are significantly increased, which subsequently switches the pro-adaptive branch of the UPR into the pro-apoptotic directly leading to neuronal loss and initiation of the neurodegenerative process.