A clinical case report of Balamuthia granulomatous amoebic encephalitis in a non-immunocompromised patient and literature review.

BACKGROUND: Balamuthia granulomatous amoebic encephalitis (GAE) is a peculiar parasitic infectious disease of the central nervous system, about 39% of the infected Balamuthia GAE patients were found to be immunocompromised and is extremely rare clinically. The presence of trophozoites in diseased tissue is an important basis for pathological diagnosis of GAE. Balamuthia GAE is a rare and highly fatal infection for which there is no effective treatment plan in clinical practice. CASE PRESENTATION: This paper reports clinical data from a patient with Balamuthia GAE to improve physician understanding of the disease and diagnostic accuracy of imaging and reduce misdiagnosis. A 61-year-old male poultry farmer presented with moderate swelling pain in the right frontoparietal region without obvious inducement three weeks ago. Head computed tomography(CT) and magnetic resonance imaging(MRI) revealed a space-occupying lesion in the right frontal lobe. Intially clinical imaging diagnosed it as a high-grade astrocytoma. The pathological diagnosis of the lesion was inflammatory granulomatous lesions with extensive necrosis, suggesting amoeba infection. The pathogen detected by metagenomic next-generation sequencing (mNGS) is Balamuthia mandrillaris, the final pathological diagnosis was Balamuthia GAE. CONCLUSION: When a head MRI shows irregular or annular enhancement, clinicians should not blindly diagnose common diseases such as brain tumors. Although Balamuthia GAE accounts for only a small proportion of intracranial infections, it should be considered in the differential diagnosis.

Exosome-transmitted ANGPTL1 suppresses angiogenesis in glioblastoma by inhibiting the VEGFA/VEGFR2/Akt/eNOS pathway.

OBJECTIVE: Glioblastoma (GBM) is a highly vascularized malignancy that relies on new vessel generation, and thus targeting angiogenesis has been a promising anti-GBM approach. ANGPTL1 is well-known for its anti-angiogenic property; nevertheless, its role in GBM is yet to be explored. Recently, the crucial role of exosomes (Exos) as intercellular communication mediators has gained prominence in GBM therapy. This work aimed to explore the role of exosomal ANGPTL1 in GBM angiogenesis and its mechanisms. METHODS: Bioinformatic analysis was performed to evaluate ANGPTL expression in GBM. Human GBM cell lines (U87 and U251) and a xenograft mouse model were employed. Exos were isolated from oe-NC- and oe-ANGPTL-transfected bone mesenchymal stem cells and identified. Cell proliferation, migration, and apoptosis were detected. Immunofluorescence, qRT-PCR, western blotting, co-immunoprecipitation, and immunohistochemistry were used to determine the molecular mechanisms underlying exosomal ANGPTL1 against GBM angiogenesis. Besides, tube generation and transmission electron microscope assays were conducted to assess GBM angiogenesis. RESULTS: Low ANGPTL1 expression was observed in GBM tumor tissues and cells. Functionally, e-ANGPTL-Exos inhibited GBM malignant progression and angiogenesis in vitro and in vivo. Mechanically, e-ANGPTL-Exos reduced VEGFA expression and blocked the VEGFR2/Akt/eNOS pathway in GBM cells and tumor tissues. Co-immunoprecipitation revealed a link between ANGPTL1 and VEGFA in GBM cells. Notably, oe-VEGFA abolished the suppressive functions of e-ANGPTL-Exos in GBM progression and angiogenesis and the VEGFR2/Akt/eNOS axis. The VEGFR2 inhibitor, vandetanib, eliminated the promotive effects of oe-VEGFA on GBM angiogenesis with suppressed VEGFR2/Akt/eNOS pathway. CONCLUSIONS: Exosomal ANGPTL1 suppressed GBM angiogenesis by inhibiting the VEGFA/VEGFR2/Akt/eNOS axis.

Update on the mechanism of microglia involvement in post-stroke cognitive impairment.

Post-stroke cognitive impairment (PSCI) is a clinical syndrome characterized by cognitive deficits that manifest following a stroke and persist for up to 6 months post-event. This condition is grave, severely compromising patient quality of life and longevity, while also imposing substantial economic burdens on societies worldwide. Despite significant advancements in identifying risk factors for PSCI, research into its underlying mechanisms and therapeutic interventions remains inadequate. Microglia, the brain's primary immune effector cells, are pivotal in maintaining, nurturing, defending, and repairing neuronal function, a process intrinsically linked to PSCI's progression. Thus, investigating microglial activation and mechanisms in PSCI is crucial. This paper aims to foster new preventive and therapeutic approaches for PSCI by elucidating the roles, mechanisms, and characteristics of microglia in the condition.

Transcranial Magnetic Stimulation in Disorders of Consciousness: An Update and Perspectives.

Disorders of consciousness (DOC) is a state in which consciousness is affected by brain injuries, leading to dysfunction in vigilance, awareness, and behavior. DOC encompasses coma, vegetative state, and minimally conscious state based on neurobehavioral function. Currently, DOC is one of the most common neurological disorders with a rapidly increasing incidence worldwide. Therefore, DOC not only impacts the lives of individuals and their families but is also becoming a serious public health threat. Repetitive transcranial magnetic stimulation (rTMS) can stimulate electrical activity using a pulsed magnetic field in the brain, with great value in the treatment of chronic pain, neurological diseases, and mental illnesses. However, the clinical application of rTMS in patients with DOC is debatable. Herein, we report the recent main findings of the clinical therapeutics of rTMS for DOC, including its efficacy and possible mechanisms. In addition, we discuss the potential key parameters (timing, location, frequency, strength, and secession of rTMS applications) that affect the therapeutic efficiency of rTMS in patients with DOC. This review may help develop clinical guidelines for the therapeutic application of rTMS in DOC.