Sirtuin 5 (SIRT5) Suppresses Tumor Growth by Regulating Mitochondrial Metabolism and Synaptic Remodeling in Gliomas.

Sirtuin 5 (SIRT5) is increasingly recognized as a key regulator of cellular metabolism, which is commonly dysregulated in cancer cells, resulting in enhanced proliferation and tumor progression. To investigate the clinicopathologic implications of SIRT5 dysregulation in glioblastoma, we performed comprehensive analyses of transcriptomic data and functional verifications using in vitro and in vivo glioblastoma models. We found that higher SIRT5 expression levels were associated with a favorable prognosis in glioma patients.

Acute calcitriol treatment mitigates vitamin D deficiency-associated mortality after intracerebral haemorrhage.

Objective: Vitamin D deficiency (VDD) is emerging as a predictor of poor prognosis in various neurological conditions, where clinical outcomes are often worse in stroke patients with VDD. This study aimed to provide experimental evidence on whether and how pre-existing VDD would affect survival and neurofunctional outcomes in intracerebral haemorrhage (ICH), and to evaluate whether acute vitamin D (VD) supplementation would improve post-stroke outcomes.

Methods: Experimental ICH models were induced in mice with and without VDD.

Harnessing the potential of large language models in medical education: promise and pitfalls.

Objectives: To provide balanced consideration of the opportunities and challenges associated with integrating Large Language Models (LLMs) throughout the medical school continuum.

Process: Narrative review of published literature contextualized by current reports of LLM application in medical education.

Conclusions: LLMs like OpenAI's ChatGPT can potentially revolutionize traditional teaching methodologies.

The duality of CXCR3 in glioblastoma: unveiling autocrine and paracrine mechanisms for novel therapeutic approaches.

Glioblastoma (GBM) is a highly aggressive brain tumor associated with limited therapeutic options and a poor prognosis. CXCR3, a chemokine receptor, serves dual autocrine-paracrine functions in cancer. Despite gaps in our understanding of the functional role of the CXCR3 receptor in GBM, it has been shown to hold promise as a therapeutic target for the treatment of GBM.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial.

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID.

Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. This pilot trial recruited long COVID patients with persistent OD.

Targeting unfolded protein response using albumin-encapsulated nanoparticles attenuates temozolomide resistance in glioblastoma.

Background: Chemoresistant cancer cells frequently exhibit a state of chronically activated endoplasmic reticulum (ER) stress. Engaged with ER stress, the unfolded protein response (UPR) is an adaptive reaction initiated by the accumulation of misfolded proteins. Protein disulfide isomerase (PDI) is a molecular chaperone known to be highly expressed in glioblastomas with acquired resistance to temozolomide (TMZ).

Prelimbic Cortical Stimulation with L-methionine Enhances Cognition through Hippocampal DNA Methylation and Neuroplasticity Mechanisms.

Declining global DNA methylation and cognitive impairment are reported to occur in the normal aging process. It is not known if DNA methylation plays a role in the efficacy of memory-enhancing therapies. In this study, aged animals were administered prelimbic cortical deep brain stimulation (PrL DBS) and/or L-methionine (MET) treatment.

Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury.

Demyelination due to oligodendrocytes loss occurs after traumatic spinal cord injury (TSCI). Several studies have suggested the therapeutic potential of vitamin D (VitD) in demyelinating diseases. However, experimental evidence in the context of TSCI is limited, particularly in the presence of prior VitD-deficiency.

Folate enzyme MTHFD2 links one-carbon metabolism to unfolded protein response in glioblastoma.

The mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) has shown oncogenic roles in various cancers and may have non-metabolic functions. This study investigated the role of MTHFD2 in glioblastoma pathogenesis. We find that MTHFD2 expression is enriched in gliomas by analysing public databases and clinical specimens.

Chaperone protein P4HB predicts temozolomide response and prognosis in malignant glioma.

Prolyl 4-hydroxylase beta polypeptide (P4HB) is a chaperone protein associated with temozolomide (TMZ) resistance through the unfolded protein response. Cancer cells with constitutive activation of endoplasmic reticulum stress and upregulation of P4HB have been observed to show resistance against chemotherapies. The present study focused on the evaluation of the prognostic value of P4HB in subtypes of glioma with or without O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation.

Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.

Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities.

Vitamin D Enhances Hematoma Clearance and Neurologic Recovery in Intracerebral Hemorrhage.

Background: Erythrophagocytosis by reparative monocyte-derived macrophage contributes to hematoma clearance and neurological recovery after intracerebral hemorrhage (ICH). Vitamin D (VitD) is a neuroprotective hormone and regulates the differentiation of monocyte-derived macrophage from monocytes. In this study, we examined the effects of VitD supplementation on monocyte-derived macrophage and hematoma clearance in rodent with ICH.

Erythrophagocytosis by Microglia/Macrophage in Intracerebral Hemorrhage: From Mechanisms to Translation.

Intracerebral hemorrhage (ICH) is a devastating condition characterized by hematoma related mass effect. Microglia/macrophage (M φ) are rapidly recruited in order to remove the red blood cells through erythrophagocytosis. Efficient erythrophagocytosis can detoxify hemolytic products and facilitate neurological recovery after ICH.

Global Survey of Demand-Side Factors and Incentives that Influence Advanced Trauma Life Support (ATLS) Promulgation.

Background: We aimed to identify and describe demand-side factors that have been used to support ATLS global promulgation, as well as current gaps in demand-side incentives.

Methods: We performed a cross-sectional survey about demand-side factors that influence the uptake and promulgation of ATLS and other trauma-related CME courses. The survey was sent to each of the four global ATLS region chiefs and 80 ATLS country directors.

ADD3 Deletion in Glioblastoma Predicts Disease Status and Survival.

Loss of heterozygosity (LOH) on chromosome 10 frequently occurs in gliomas. Whereas genetic loci with allelic deletion often implicate tumor suppressor genes, a putative tumor suppressor Adducin3 () mapped to chromosome 10q25.2 was found to be preferentially downregulated in high-grade gliomas compared with low-grade lesions.

Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma.

Glioblastoma (GBM) is the most malignant primary tumor in the central nervous system of adults. Temozolomide (TMZ), an alkylating agent, is the first-line chemotherapeutic agent for GBM patients. However, its efficacy is often limited by innate or acquired chemoresistance.

Anti-tumor effects of vitamin D in glioblastoma: mechanism and therapeutic implications.

Glioma is the most prevalent primary brain tumor in adults among which glioblastoma is the most malignant and lethal subtype. Its common resistance to conventional chemotherapeutics calls for the development of alternative or concomitant treatment. Taking advantage of its endocrine function as a neurosteroid, vitamin D has become a target of interest to be used in conjunction with different chemotherapies.

Fibrinolytic-Facilitated Chronic Subdural Hematoma Drainage-A Systematic Review.

Background: The current treatment options for chronic subdural hematoma (CSDH) include burr hole drainage, twist drill drainage, and craniotomy with or without postoperative catheter drainage. Although generally effective, these treatments have continued to be complicated by recurrence, especially in partially hemolyzed or septated hematomas. Recently, interest in the use of fibrinolytic agents as an adjunct to surgical treatment to address this limitation has been increasing.

Secondary gliosarcoma: the clinicopathological features and the development of a patient-derived xenograft model of gliosarcoma.

Background: Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown.

Vertebral-carotid bypass for common carotid artery occlusion.

One of the treatment options for long segment common carotid artery (CCA) occlusion is bypass surgery with different combinations of donors and receipts. Using vertebral artery (VA) as the donor for CCA occlusion was uncommonly reported. The reported cases were using jump graft to connect V3 segment of VA to either CCA or ICA.