Ionizing Radiation-Induced GDF15 Promotes Angiogenesis in Human Glioblastoma Models by Promoting VEGFA Expression Through p-MAPK1/SP1 Signaling.

Glioblastoma multiforme (GBM), the most aggressive cancer type that has a poor prognosis, is characterized by enhanced and aberrant angiogenesis. In addition to surgical resection and chemotherapy, radiotherapy is commonly used to treat GBM. However, radiation-induced angiogenesis in GBM remains unexplored. This study examined the role of radiation-induced growth/differentiation factor-15 (GDF15) in regulating tumor angiogenesis by promoting intercellular cross-talk between brain endothelial cells (ECs) and glioblastoma cells. Radiation promoted GDF15 secretion from human brain microvascular endothelial cells (HBMVECs). Subsequently, GDF15 activated the transcriptional promoter VEGFA in the human glioblastoma cell line U373 through p-MAPK1/SP1 signaling. Upregulation of vascular endothelial growth factor (VEGF) expression in U373 cells resulted in the activation of angiogenic activity in HBMVECs via KDR phosphorylation. Wound healing, tube formation, and invasion assay results revealed that the conditioned medium of recombinant human GDF15 (rhGDF15)-stimulated U373 cell cultures promoted the angiogenic activity of HBMVECs. In the HBMVEC-U373 cell co-culture, GDF15 knockdown mitigated radiation-induced VEGFA upregulation in U373 cells and enhanced angiogenic activity of HBMVECs. Moreover, injecting rhGDF15-stimulated U373 cells into orthotopic brain tumors in mice promoted angiogenesis in the tumors. Thus, radiation-induced GDF15 is essential for the cross-talk between ECs and GBM cells and promotes angiogenesis. These findings indicate that GDF15 is a putative therapeutic target for patients with GBM undergoing radio-chemotherapy.

Circadian fluctuations in three types of sensory modules in healthy subjects.

This study was designed to observe and compare the circadian fluctuations in tactile sense, joint reposition sense and two-point discrimination in healthy subjects. Twenty-one healthy adult subjects received perceptual ability tests through these three different sensory modules at approximately 9:00, 13:00 and 18:00 in a day. The distribution of ranking for perceptual ability was significantly different among the three different time points in each individual, with highest perceptual ability in the evening compared with noon and morning, in terms of tactile sense and two-point discrimination. These findings suggest that the perceptual ability of healthy subjects fluctuates according to the time points in a day.

Long-term Outcome of Motor Function in a Child with Moyamoya Disease: A Case Report.

[Purpose] This observational study provides a retrospective description of changes in motor function of a 10 year old child who suffered from motor weakness caused by Moyamoya disease (MMD) over an approximately 3 year follow-up observation period. [Methods] The child was diagnosed as MMD due to multifocal encephalomalacia in both frontal and parietal cortices. After the ischemic attack, the child received physical therapy the based on stroke rehabilitation, including muscle strengthening exercises, training of functional activity/ADL, and neurodevelopmental treatment. [Results] The child's MRI showed areas of ischemic infarction in both the frontal and parietal lobes. Steno-occlusive findings for both the anterior cerebral artery and middle cerebral artery were observed on cerebral angiography. Regarding changes of motor function during the three-year follow-up, significant improvements, in the Motricity index, Modified Brunnstrom Classification, manual function test, and functional ambulatory category were observed. [Conclusion] The basic motor function and functional abilities of the child showed improvement with conservative treatment over approximately three years. The functional motor ability of children with MMD may be similar to the recovery progression of pediatric stroke patients, if there is no re-occurrence of ischemia.

Identification of cortical activation and white matter architecture according to short-term motor learning in the human brain: functional MRI and diffusion tensor tractography study.

OBJECTIVES: The purpose of this study was to examine whether two weeks of short-term motor training led to changes of cortical activation patterns and white matter integrity in cortical and subcortical structures according to motor skill acquisition, using functional MRI (fMRI) and diffusion tensor image (DTI). METHODS: We enrolled twenty healthy volunteers, who were randomly assigned to training and control groups. The training group was trained with a serial reaction time (SRT) task, one hour a day for 10 days within two weeks, whereas the control group had no training. Movement accuracy (MA) and movement time (MT) were tested twice before and after training, while fMRI was scanned during SRT task. Immediately after these tests, DTI was conducted. RESULTS: The training group showed significant differences in the increase of MA and the reduction of MT, compared with control group. The activated volume of cortices related to motor function was gradually decreased in the training group, according to motor skill acquisition. DTI analysis showed no significant differences between pre- and post-tests in both groups. CONCLUSIONS: Our findings indicated that short-term motor training led to cortical activation patterns of the cerebral cortex according to implicit motor learning. However, changes of white matter integrity were not observed. It seems that short-term motor training may not be enough to change white matter architectures, due to lack of the training period.

Microstructure and hardness of nano-sized Fe-based self-fluxing alloy powder with SiC particles.

The Fe-based self-fluxing alloy powders and SiC particles were mixed and milled by high energy ball-milling, and their microstructure and micro-hardness were investigated after subsequent compaction and sintering. The initial alloy powders with a mean size of approximately 80 microm were fined to 2.1 microm after milling at 800 rpm for 5 h. However, the powder mixture of alloy powder and SiC particle showed much larger powder size compared to the initial alloy powders. The bulk composites were obtained from the powder mixture by compaction under a pressure of 800 MPa for 10 min and sintering at 1073 K for 3 h. The composites had much higher micro-hardness of more than 700 Hv compared to alloy powder. The micro-hardness of composites slightly increased with the content of SiC particles.

Brain activation pattern according to exercise complexity: a functional MRI study.

The aim of this study was to compare the areas of brain activation between complex and simple exercises in a unimanual hand and to assess the possibility of an exercise task for paretic hands following stroke. The subjects included 11 healthy right-handed volunteers. The complex exercise was a wooden ball rotation task with the unimanual hand and the simple exercise was a hand grasp task performed during a functional MRI scan. Stronger activation of the left primary sensorimotor cortex, the left premotor area, and the ipsilateral cerebellum emerged when the complex movement was performed. Ipsilateral activity was located in the primary sensory cortex and premotor area, and contralateral activity was shown in the left cerebellum. These results suggest that a unimanual ball rotation task may be appropriate for rehabilitation of a movable paretic hand in an early stage of stroke recovery, which should provide motor and sensory input using external stimuli, while the simple motor task may appropriate in a compensatory stage, and should inhibit the ipsilateral activity due to maladaptive plasticity.