Transthoracic Ultrasound Improves Cardiac Function in Mice.

Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been researched is the electrical stimulation of the vagus nerve to exert cardio protection. This method has been shown to reduce the systemic inflammatory response and maintain the immune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation (US) of the vagus nerve to alleviate cardiac dysfunction caused by lipopolysaccharide (LPS). We developed a noninvasive transthoracic US system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 h after LPS treatment. Results showed that daily heart targeting US for 4 days significantly increased left ventricular systolic function ( p = 0.01) and improved ejection fraction ( p = 0.03) and shortening fraction ( p = 0.04). Furthermore, US significantly reduced inflammation cytokines, including IL-6 ( p = 0.03) and IL- 1ß ( p = 0.04). In addition, cervical vagotomy abrogated the effect of US, suggesting the involvement of the vagus nerve's anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest the potential of transthoracic US as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function and provide new targets for rehabilitation of peripheral organ function.

Ultrasound Stimulation of Prefrontal Cortex Improves Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice.

Increasing evidence indicates that inflammatory responses may influence brain neurochemical pathways, inducing depressive-like behaviors. Ultrasound stimulation (US) is a promising non-invasive treatment for neuropsychiatric diseases. We investigated whether US can suppress inflammation and improve depressive-like behaviors. Mice were intraperitoneally injected with lipopolysaccharide to induce depressive-like behaviors. Ultrasound wave was delivered into the prefrontal cortex (PFC) for 30 min. Depressive- and anxiety-like behaviors were evaluated through the forced swimming test (FST), tail suspension test (TST), and elevated plus maze (EPM). Biochemical analyses were performed to assess the expression of inflammatory cytokines in the PFC and serum. The results indicated that US of the PFC significantly improved depressive-like behaviors in the TST (p < 0.05) and FST (p < 0.05). Anxiety-like behaviors also improved in the EPM (p < 0.05). Furthermore, the lipopolysaccharide-mediated upregulation of IL-6, IL-1ß, and TNF-α in the PFC was significantly reduced (p < 0.05) by US. In addition, no tissue damage was observed. Overall, US of PFC can effectively improve lipopolysaccharide-induced depressive-like behaviors, possibly through the downregulation of inflammatory cytokines in the PFC. US may be a safe and promising tool for improvement of depression.

MicroRNA 223 Targeting ATG16L1 Affects Microglial Autophagy in the Kainic Acid Model of Temporal Lobe Epilepsy.

This study aimed to explore whether microRNA (miR) 223 affects microglial autophagy by targeting autophagy-related 16-like 1 (ATG16L1) in the kainic acid (KA) model of temporal lobe epilepsy (TLE). The miRNA and mRNA expression levels were quantified using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression was investigated using western blotting. A dual-luciferase reporter assay was used to test the direct interaction between miR 223 and ATG16L1. In situ hybridization was performed to measure the hippocampal expression of miR 223. We used immunofluorescence staining to assess the expression of ATG16L1 and microtubule-associated protein light chain 3 (LC3) in the murine hippocampal microglia. Inhibitor of miR 223 was utilized to investigate the role of miR 223 in TLE, and the epileptic activity was assessed using electroencephalography (EEG). The autophagosomes were observed by transmission electron microscopy. In patients with TLE, the murine KA model of TLE, and the KA-stimulated BV2 cells, miR 223, and sequestosome 1 (SQSTM1/P62) expressions were remarkably increased, whereas ATG16L1 and LC3 levels were significantly decreased. Using a dual-luciferase reporter assay, ATG16L1 was determined as a direct target of miR 223. Treatment with antagomir 223 alleviated epilepsy, prevented abnormalities in EEG recordings and increased the ATG16L1 and LC3 levels in KA-treated mice. Inhibition of miR 223 induced increased autophagy in BV2 cells upon Rapamycin stimulation. These findings show that miR 223 affects microglial autophagy via ATG16L1 in the KA model of TLE. The miR 223/ATG16L1 pathway may offer a new treatment option for TLE.

Immune response in glioma's microenvironment.

OBJECTIVES: Glioma is the most common tumor of the central nervous system. In this review, we outline the immunobiological factors that interact with glioma cells and tumor microenvironment (TME), providing more potential targets for clinical inhibition of glioma development and more directions for glioma treatment. CONTENT: Recent studies have shown that glioma cells secrete a variety of immune regulatory factors and interact with immune cells such as microglial cells, peripheral macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes in the TME. In particular, microglia plays a key role in promoting glioma growth. Infiltrating immune cells induce local production of cytokines, chemokines and growth factors. Further leads to immune escape of malignant gliomas. SUMMARY AND OUTLOOK: The complex interaction of tumor cells with the TME has largely contributed to tumor heterogeneity and poor prognosis. We review the immunobiological factors, immune cells and current immunotherapy of gliomas, provide experimental evidence for future research and treatment of gliomas.