Disrupted HSF1 regulation in normal and exceptional brain aging.

Brain aging is a major risk factor for cognitive diseases such as Alzheimer's disease (AD) and vascular dementia. The rate of aging and age-related pathology are modulated by stress responses and repair pathways that gradually decline with age. However, recent reports indicate that exceptional longevity sustains and may even enhance the stress response.

A simplified and sensitive immunoprecipitation approach for the analysis of HSF1 in murine liver tissue.

Heat shock factor 1, HSF1, is one of several family members that recognize repeated nGAAn sequences associated with the heat shock element of heat shock and other genes. This transactivator is activated from a monomeric to trimeric form by oxidative, thermal and other stressors. Various studies show that HSF1 levels increase with cancer and decrease with aging and neurodegenerative disorders.

Augmentation of the heat shock axis during exceptional longevity in Ames dwarf mice.

How the heat shock axis, repair pathways, and proteostasis impact the rate of aging is not fully understood. Recent reports indicate that normal aging leads to a 50% change in several regulatory elements of the heat shock axis. Most notably is the age-dependent enhancement of inhibitory signals associated with accumulated heat shock proteins and hyper-acetylation associated with marked attenuation of heat shock factor 1 (HSF1)-DNA binding activity.

A molecular perspective on age-dependent changes to the heat shock axis.

Aging is a complex process associated with progressive damage that leads to cellular dysfunction often accompanied by frailty and age-related diseases. Coping with all types of physiologic stress declines with age. While representing a primordial, cross-species response in poikilo- and homeotherms, the age-dependent perturbation of the stress response is more complex than previously thought.

Multifactorial Attenuation of the Murine Heat Shock Response With Age.

Age-dependent perturbation of the cellular stress response affects proteostasis and other key functions relevant to cellular action and survival. Central to age-related changes in the stress response is loss of heat shock factor 1 (HSF1)-DNA binding and transactivation properties. This report elucidates how age alters different checkpoints of HSF1 activation related to posttranslational modification and protein interactions.

Graphene Oxide-Based Biocompatible 3D Mesh with a Tunable Porosity and Tensility for Cell Culture.

One of the major challenges associated with modeling the influence of the cellular microenvironment on cell growth and differentiation is finding suitable substrates for growing the cells in a manner that recapitulates the cell-cell and cell-microenvironmental interactions in vitro. As one approach to address this challenge, we have developed graphene oxide (GO)-3D mesh with tunable hardness and porosity for application in cell culture systems. The synthetic method of GO-3D mesh is simple, easily reproducible, and low cost.

Anti-Leukemic Activity of Shikonin: Role of ERP57 in Shikonin Induced Apoptosis in Acute Myeloid Leukemia.

Background/aims: ER-Stress and activation of unfolded protein response belong to the major factors involved in chemoresistance in cancer cells. In this study we investigated the effect of shikonin on the survival of acute myeloid leukemia cells and the role of ER-stress protein ERP57, a protein disulfide isomerase, in improvement of chemotherapy.

Methods: Using MTT assay we studied cytotoxic effects of shikonin on HL-60 cells.

The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits.

Inhibition of STAT3, FAK and Src mediated signaling reduces cancer stem cell load, tumorigenic potential and metastasis in breast cancer.

Cancer stem cells (CSCs) are responsible for aggressive tumor growth, metastasis and therapy resistance. In this study, we evaluated the effects of Shikonin (Shk) on breast cancer and found its anti-CSC potential. Shk treatment decreased the expression of various epithelial to mesenchymal transition (EMT) and CSC associated markers.

Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.

Resistance to chemotherapeutic drugs is the major hindrance in the successful cancer therapy. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family of ligands, which initiates apoptosis in cancer cells through interaction with the death receptors DR4 and DR5. TRAIL is perceived as an attractive chemotherapeutic agent as it specifically targets cancer cells while sparing the normal cells.

(6)-Gingerolinduced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression.

The natural polyphenolic alkanone (6)-gingerol (6G) has established anti-inflammatory and antitumoral properties. However, its precise mechanism of action in myeloid leukemia cells is unclear. In this study, we investigated the effects of 6G on myeloid leukemia cells in vitro and in vivo.