Role of Nucleobindin-2 in the Clinical Pathogenesis and Treatment Resistance of Glioblastoma.

Glioblastoma (GBM) stands as the most prevalent primary malignant brain tumor, typically resulting in a median survival period of approximately thirteen to fifteen months after undergoing surgery, chemotherapy, and radiotherapy. Nucleobindin-2 (NUCB2) is a protein involved in appetite regulation and energy homeostasis. In this study, we assessed the impact of NUCB2 expression on tumor progression and prognosis of GBM. We further evaluated the relationship between NUCB2 expression and the sensitivity to chemotherapy and radiotherapy in GBM cells. Additionally, we compared the survival of mice intracranially implanted with GBM cells. High NUCB2 expression was associated with poor prognosis in patients with GBM. Knockdown of NUCB2 reduced cell viability, migration ability, and invasion ability of GBM cells. Overexpression of NUCB2 resulted in reduced apoptosis following temozolomide treatment and increased levels of DNA damage repair proteins after radiotherapy. Furthermore, mice intracranially implanted with NUCB2 knockdown GBM cells exhibited longer survival compared to the control group. NUCB2 may serve as a prognostic biomarker for poor outcomes in patients with GBM. Additionally, NUCB2 not only contributes to tumor progression but also influences the sensitivity of GBM cells to chemotherapy and radiotherapy. Therefore, targeting NUCB2 protein expression may represent a novel therapeutic approach for the treatment of GBM.

Therapeutic Effect of Mitochondrial Division Inhibitor-1 (Mdivi-1) on Hyperglycemia-Exacerbated Early and Delayed Brain Injuries after Experimental Subarachnoid Hemorrhage.

Background: Neurological deficits following subarachnoid hemorrhage (SAH) are caused by early or delayed brain injuries. Our previous studies have demonstrated that hyperglycemia induces profound neuronal apoptosis of the cerebral cortex. Morphologically, we found that hyperglycemia exacerbated late vasospasm following SAH. Thus, our previous studies strongly suggest that post-SAH hyperglycemia is not only a response to primary insult, but also an aggravating factor for brain injuries. In addition, mitochondrial fusion and fission are vital to maintaining cellular functions. Current evidence also shows that the suppression of mitochondrial fission alleviates brain injuries after experimental SAH. Hence, this study aimed to determine the effects of mitochondrial dynamic modulation in hyperglycemia-related worse SAH neurological prognosis. Materials and methods: In vitro, we employed an enzyme-linked immunosorbent assay (ELISA) to detect the effect of mitochondrial division inhibitor-1 (Mdivi-1) on lipopolysaccharide (LPS)-induced BV-2 cells releasing inflammatory factors. In vivo, we produced hyperglycemic rats via intraperitoneal streptozotocin (STZ) injections. Hyperglycemia was confirmed using blood-glucose measurements (>300 mg/dL) 7 days after the STZ injection. The rodent model of SAH, in which fresh blood was instilled into the craniocervical junction, was used 7 days after STZ administration. We investigated the mechanism and effect of Mdivi-1, a selective inhibitor of dynamin-related protein (Drp1) to downregulate mitochondrial fission, on SAH-induced apoptosis in a hyperglycemic state, and evaluated the results in a dose−response manner. The rats were divided into the following five groups: (1) control, (2) SAH only, (3) Diabetes mellitus (DM) + SAH, (4) Mdivi-1 (0.24 mg/kg) + DM + SAH, and (5) Mdivi-1 (1.2 mg/kg) + DM + SAH. Results: In vitro, ELISA revealed that Mdivi-1 inhibited microglia from releasing inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. In vivo, neurological outcomes in the high-dose (1.2 mg/kg) Mdivi-1 treatment group were significantly reduced compared with the SAH and DM + SAH groups. Furthermore, immunofluorescence staining and ELISA revealed that a high dose of Mdivi-1 had attenuated inflammation and neuron cell apoptosis by inhibiting Hyperglycemia-aggravated activation, as well as microglia and astrocyte proliferation, following SAH. Conclusion: Mdivi-1, a Drp-1 inhibitor, attenuates cerebral vasospasm, poor neurological outcomes, inflammation, and neuron cell apoptosis following SAH + hyperglycemia.

Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Correlation With CD4 Levels in a Patient With HIV Infection.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare tumor found in immunocompromised patients, and its treatment is not well-established. A role for antiretroviral therapy in human immunodeficiency virus (HIV)-related EBV-SMT has been proposed; however, the relevance of tumor size, CD4 levels, and immune reconstitution inflammatory syndrome (IRIS) has not been previously reported. We present the first case, to our knowledge, of a tumor that shrank in association with elevated CD4 counts. IRIS occurred in this case following antiretroviral therapy. This finding highlights the importance of the immune response in HIV-related EBV-SMT.

Medulla oblongata germinoma with Klinefelter syndrome.

Intracranial germinomas mostly occur in teenagers and young adults. The common sites are pineal and suprasellar regions. Males with Klinefelter syndrome, compared with males without chromosomal abnormalities, are known to have a higher incidence of developing pineal or suprasellar germinomas. As for germinoma in the medulla oblongata, this is rare, with only 21 previous cases reported. Due to the rarities, any relationship between people with Klinefelter syndrome and medulla oblongata germinomas remains undetermined. We present a rare case of medulla oblongata germinoma in a 25-year-old man. It is the second case of medulla oblongata germinoma in association with Klinefelter syndrome. We emphasize the importance of karyotyping in every case of germinoma, especially those with intracranial germinomas at atypical locations.