Downregulating DNA methyltransferase 3B by suppressing the PI3K/Akt signaling pathway enhances the chemosensitivity of glioblastoma to temozolomide.

Glioblastoma (GBM) is the most common malignant brain tumor and has the poorest prognosis attributed to its chemoresistance to temozolomide (TMZ), the first-line drug for treating GBM. TMZ resistance represents a significant obstacle to successful GBM treatment, necessitating the development of new strategies to overcome this resistance and augment the chemosensitivity of GBM cells to TMZ. This study established a TMZ-resistant U251 (U251-TMZ) cell line by exposing it to increasing doses of TMZ in vitro. We focused on the DNA methyltransferase 3B (DNMT3B) gene, phosphorylated Akt (p-Akt), total Akt (t-Akt), phosphorylated PI3K (p-PI3K), and total PI3K (t-PI3K) protein expression. Results showed that the DNMT3B gene was significantly upregulated in the U251-TMZ cell line. The p-Akt and p-PI3K protein expression in U251-TMZ cells was also significantly elevated. Moreover, we found that DNMT3B downregulation was correlated with the increased chemosensitivity of GBM cells to TMZ. LY294002 suppressed the PI3K/Akt signaling pathway, leading to a notable inhibition of PI3K phosphorylation and a significant decrease in DNMT3B expression in U251-TMZ cells. Given that DNMT3B expression is mediated by the PI3K/Akt signaling pathway, its downregulation further increased the chemosensitivity of GBM cells to TMZ and therefore is a promising therapeutic for GBM treatment. Our results suggested that DNMT3B downregulation can inhibit the proliferation of GBM cells and induce GBM cell apoptosis in vitro. In addition, the PI3K/Akt signaling pathway plays an important role in the chemosensitivity of GBM cells to TMZ by regulating DNMT3B expression.

Frequency-specific equivalence of brain activity on motor imagery during action observation and action execution.

BACKGROUND: Human motor imagery (MI), action execution, and action observation (AO) are functionally considered as equivalent. MI during AO can extensively induce activation of motor-related brain network in the absence of overt movement. The magnetoencephalography (MEG) provides an important technology to reveal and reflect human brain information processing in multi-frequency bands. Utilizing a MEG system, we aimed to quantitatively investigate the frequency-specific equivalent characteristics in brain processing patterns between MI during AO and action execution in multi-frequency bands, including delta, theta, alpha, beta, gamma, and high-frequency oscillations. METHODS: A total of 12 healthy subjects were studied with a whole-head MEG system during finger movement and MI during finger movement observation. We analyzed the brain activities in multi-frequency ranges of 1 Hz to 200 Hz. RESULTS: Both MI during AO and action execution evoked the distinctive brain activities in low frequency ranges (i.e. delta, theta, and alpha). Significant differences were found in global spectral power between finger movement and MI during AO in delta and alpha oscillations. Compared with finger movement, delta (1-4 Hz) oscillation power in MI during AO were obviously decreased in left and right frontals and occipitals, and theta (4-8 Hz) and alpha (8-13 Hz) oscillation power were obviously increased in frontal, parietal and occipital. CONCLUSION: MEG power evoked by finger movement and MI during AO is mainly concentrated in the energy distribution below 13 Hz. Furthermore, finger movement and MI during AO might share frequency-specific equivalence of brain neural activation dependent on different MEG frequency ranges.

Effect of Hormone Levels and Aging on Cognitive Function of Patients with Pituitary Adenomas Prior to Medical Treatment.

BACKGROUND: Cognitive impairments have been reported in patients with pituitary adenomas (PAs). The aim of this research was to demonstrate the effects of hormones and age on cognitive decline in patients with PAs. METHODS: A total of 64 patients with PA and 69 healthy control subjects (HCs) were recruited for this study. Both PAs and HCs were divided into a younger group (<50 years of age) and an older group (≥50 years of age). Neurocognitive domains were assessed using the Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC) tests. Furthermore, we also investigated the relationship between cognitive domains and tumor volume, and the hormone levels and age of patients with PA. RESULTS: Several of the cognitive impairments found on the WAIS-RC and WMS-RC tests were more frequently observed in untreated patients with PA. Importantly, no significant correlations were found between cognitive domains and tumor volume after controlling age, sex, and educational levels. Furthermore, several significant correlations were found between cognitive domains and hormone levels, such as free thyroxine and adrenocorticotropic hormone, after controlling age, sex, and educational levels. Finally, the age of the patients was found to correlate with a decrease in memory after controlling sex and educational levels. CONCLUSIONS: Our findings demonstrate a significant decline in the cognitive performance of patients with PA prior to medical treatment, especially in older patients, which suggests that hormones and age have the ability to interact and aggravate cognitive decline in patients with PA.

Histopathologic and Clinical Correlation of Aberrant Neuromagnetic Activities with Low to High Frequency of Gliomas.

OBJECTIVE: To quantify the low- to high-frequency range of abnormal brain activities and assess the histopathologic and clinical correlation in patients with glioma. METHODS: Twenty-five patients with glioma and 20 healthy controls were examined with a magnetoencephalography (MEG) system. MEG data collected in 6 frequency bands, including 1-4 Hz, 4-8 Hz, 8-12 Hz, 12-30 Hz, 30-45 Hz, and 55-75 Hz, were analyzed by neuropathology to assess neuromagnetic signatures of glioma grade. RESULTS: Compared with controls, patients with glioma showed greatly altered brain activities in 4-8 Hz, 8-12 Hz, and 55-75 Hz. Magnetic source power of brain activities in 4-8 Hz and 55-75 Hz in patients with high-grade gliomas significantly differed from that in patients with low-grade gliomas. The magnitude of source power of brain activities in 4-8 Hz and 55-75 Hz had marked correlation with the grading of gliomas in histopathological analyses. CONCLUSIONS: The degree of neuromagnetic source abnormality is a potential biomarker for noninvasive assessment of glioma grade. Because MEG tests can be performed noninvasively and preoperatively, MEG may play an important role in clinical biopsies and surgical planning for patients with brain gliomas in the future.