Therapeutically engineered stem cells have shown promise for glioblastoma multiforme (GBM) therapy; however, key preclinical studies are urgently needed for their clinical translation. In this study, we investigated a new approach to GBM treatment using therapeutic stem cells encapsulated in biodegradable, synthetic extracellular matrix (sECM) in mouse models of human GBM resection. Using multimodal imaging, we first showed quantitative surgical debulking of human GBM tumors in mice, which resulted in increased survival. Next, sECM encapsulation of engineered stem cells increased their retention in the tumor resection cavity, permitted tumor-selective migration and release of diagnostic and therapeutic proteins in vivo. Simulating the clinical scenario of GBM treatment, the release of tumor-selective S-TRAIL (secretable tumor necrosis factor apoptosis inducing ligand) from sECM-encapsulated stem cells in the resection cavity eradicated residual tumor cells by inducing caspase-mediated apoptosis, delayed tumor regrowth and significantly increased survival of mice. This study demonstrates the efficacy of encapsulated therapeutic stem cells in mouse models of GBM resection and may have implications for developing effective therapies for GBM.
This review describes the complex relationships between depression, anxiety, and bipolar disorder with atherosclerosis by discussing epidemiological evidence, implicated mechanisms, and the impact of psychiatric interventions on cardiovascular outcomes. Depression, anxiety, and bipolar disorder convey independent risk for atherosclerosis. Further, the presence of cardiovascular disease often contributes to worsened psychiatric symptoms. Current evidence supports a rising prevalence of psychiatric disorders in association with atherosclerosis and demographic disparities, with stronger links in women and African Americans. Shared biological mechanisms include autonomic dysfunction, hypothalamic-pituitary-adrenal axis overactivity, inflammation, and vascular effects. Pharmacological treatments and behavioral therapies, such as psychotherapy, have the potential to reduce cardiovascular events and improve physiological markers. The expanding understanding of the bidirectional link between depression, anxiety, and bipolar disorder and atherosclerosis calls for integrated care. Early screening and management of these psychiatric disorders may help to slow cardiovascular disease progression.
Disorders of gut-brain interaction (DGBI; formerly known as functional gastrointestinal disorders) are chronic gastrointestinal conditions with no objective biomarker. DGBI such as irritable bowel syndrome and functional dyspepsia are common in eating disorders (EDs) and may maintain ED behaviors including restriction and purging, but DGBI symptoms are not explicitly addressed in standard ED treatments. This review aims to summarize pharmacological, behavioral, and nutritional support interventions for DGBI that may be beneficial in managing DGBI symptoms in individuals with EDs. DGBI symptoms are common in EDs, including shape/weight-motivated EDs (e.g., anorexia nervosa) and in avoidant/restrictive food intake disorder. Theoretical work supports bi-directional risk. While evidence-based treatments for DGBI symptoms are available, there is limited research on treatment of DGBI within the context of an ED. Neuromodulator medications, brain-gut behavioral therapies (BGBTs), and nutritional support may help manage DGBI symptoms in EDs, but currently only retrospective chart reviews and case studies support this approach. DGBI symptoms are frequently present in patients with EDs and could be an important maintaining factor for ED symptoms but further prospective research is needed. DGBI management techniques have not been well-studied in ED populations. Future research may consider adapting interventions for DGBI in ED populations.
This review synthesizes the key scientific discussions and clinical insights presented at the Core Conference of GlomCon Hawaii 2025, held in Oahu, Hawaii, from September 23–25, 2025.
Neuromuscular junction (NMJ) disruption is an early pathogenic event in amyotrophic lateral sclerosis (ALS). Yet, direct links between NMJ pathways and ALS-associated genes such as FUS, whose heterozygous mutations cause aggressive forms of ALS, remain elusive. In a knock-in Fus-ALS mouse model, we identified postsynaptic NMJ defects in newborn homozygous mutants that were attributable to mutant FUS toxicity in skeletal muscle. Adult heterozygous knock-in mice displayed smaller neuromuscular endplates that denervated before motor neuron loss, which is consistent with 'dying-back' neuronopathy. FUS was enriched in subsynaptic myonuclei, and this innervation-dependent enrichment was distorted in FUS-ALS. Mechanistically, FUS collaborates with the ETS transcription factor ERM to stimulate transcription of acetylcholine receptor genes. Co-cultures of induced pluripotent stem cell-derived motor neurons and myotubes from patients with FUS-ALS revealed endplate maturation defects due to intrinsic FUS toxicity in both motor neurons and myotubes. Thus, FUS regulates acetylcholine receptor gene expression in subsynaptic myonuclei, and muscle-intrinsic toxicity of ALS mutant FUS may contribute to dying-back motor neuronopathy.
