Alteration in brain functional connectivity in patients with post-stroke cognitive impairment during memory task: A fNIRS study.

OBJECTIVE: This study attempted to evaluate the functional connectivity (FC) in relevant cortex areas during three memory tasks using the functional near-infrared spectroscopy (fNIRS) method to expound the neural mechanisms in individuals with post-stroke cognitive impairment (PSCI). METHODS: Short-term memory and visuospatial abilities were assessed using the clock drawing test, digit span test, and Corsi Block-tapping tests with simultaneous fNIRS. The oxygenated hemoglobin concentration signals were recorded from the bilateral motor sense cortex (LMS/RMS) and prefrontal lobe (LPFT/PFT/RPFT) of 19 subjects with cognitive impairment (PSCI group), 27 stroke subjects (STR group) and 26 healthy subjects (HC group). RESULTS: MMSE scores were positively correlated with the clock drawing test and digit span test scores but not with Corsi Block-tapping scores. During each test, functional connectivity between the bilateral MS (LMS/RMS) was highest within each group, but the functional connectivity between motor sense cortex and frontal lobe was lowest. PSCI group showed decreased FC between bilateral motor sense cortex (P < 0.05) and between motor sense cortex and frontal lobe (P > 0.05) during clock drawing test and Corsi Block-tapping test while decreased FC between each region of interest during digit span test with no significant difference. Functional connectivity levels were closely related to MMSE scores. CONCLUSIONS: Decreased functional connectivity level may be a marker of impaired cognitive function in post-stroke cognitive impairment. The fNIRS-based functional connectivity provides a non-invasive method to recognize cognitive impairment post-stroke. Functional connectivity changes may help to further understand the neural mechanisms of cognitive impairment post stroke.

Low frequency vibrating magnetic field-triggered magnetic microspheres with a nanoflagellum-like surface for cancer therapy.

BACKGROUND: The magneto-mechanical force killing cancer cells is an interesting and important strategy for cancer therapy. RESULTS: Novel magnetic microspheres composed of a Fe3O4 nanocore, a bovine serum albumin (BSA) matrix, and a rod-like SiO2 nanoshell, which had flagellum-like surface for force-mediated cancer therapy were developed. One such magnetic microsphere (Fe3O4/BSA/rSiO2) at a cancer cell (not leave the cell surface) under a low frequency vibrating magnetic field (VMF) could generate 6.17 pN force. Interestingly, this force could induce cancer cell to generate reactive oxygen species (ROS). The force and force-induced ROS could kill cancer cells. The cell killing efficiency of Fe3O4/BSA/rSiO2 exposed to a VMF was enhanced with increasing silica nanorod length, and the microspheres with straight nanorods exhibited stronger cell killing ability than those with curled nanorods. Fe3O4/BSA/rSiO2 triggered by a VMF could efficiently inhibit mouse tumor growth, while these microspheres without a VMF had no significant effect on the cell cycle distribution, cell viability, tumor growth, and mouse health. CONCLUSIONS: These microspheres with unique morphological characteristics under VMF have great potential that can provide a new platform for treating solid tumors at superficial positions whether with hypoxia regions or multidrug resistance.

Genetic ablation of TAZ induces HepG2 liver cancer cell apoptosis through activating the CaMKII/MIEF1 signaling pathway.

BACKGROUND AND OBJECTIVE: Transcriptional coactivator with PDZ-binding motif (TAZ) has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of TAZ and mitochondrial homeostasis in liver cancer viability have not been explored. The aim of our study was to investigate the influence of TAZ on HepG2 liver cancer cell apoptosis. MATERIALS AND METHODS: HepG2 liver cancer cell was used in the present study, and shRNA against TAZ was transfected into HepG2 cell to knockdown TAZ expression. Mitochondrial function was analyzed using Western blotting, immunofluorescence assay, and flow cytometry. Pathway blocker was used to confirm the role of CaMKII pathway in TAZ-mediated cancer cell death. RESULTS: Our results indicated that TAZ deletion induced death in HepG2 cell via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, were activated by TAZ deletion. Furthermore, we found that TAZ affected mitochondrial stress by triggering mitochondrial elongation factor 1 (MIEF1)-related mitochondrial dysfunction. The loss of MIEF1 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that TAZ regulated MIEF1 expression via the CaMKII signaling pathway. Blockade of the CaMKII pathway prevented TAZ-mediated MIEF1 upregulation and improved cancer cell survival. CONCLUSION: Taken together, our results highlight the key role of TAZ as a master regulator of HepG2 liver cancer cell viability via the modulation of MIEF1-related mitochondrial stress and the CaMKII signaling pathway. These findings define TAZ and MIEF1-related mitochondrial dysfunction as tumor suppressors that act by promoting cancer apoptosis via the CaMKII signaling pathway, with potential implications for new approaches to liver cancer therapy.