Morinda officinalis oligosaccharides alleviate depressive-like behaviors in post-stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation.

AIMS: Morinda officinalis oligosaccharides (MOOs), a traditional Chinese medicine, have been used to treat mild and moderate depressive episodes. In this study, we investigated whether MOOs can ameliorate depressive-like behaviors in post-stroke depression (PSD) rats and further explored its mechanism by suppressing microglial NLRP3 inflammasome activation to inhibit hippocampal inflammation. METHODS: Behavioral tests were performed to evaluate the effect of MOOs on depressive-like behaviors in PSD rats. The effects of MOOs on the expression of IL-18, IL-1ß, and nucleotide-binding domain leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3) inflammasome were measured in both PSD rats and lipopolysaccharide (LPS) and adenosine triphosphate (ATP) stimulated primary rat microglia by reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence and Western blot analysis. Adeno-associated virus (AAV) was injected into the hippocampus to regulate NLRP3 inflammasome expression. The detailed molecular mechanism underlying the effects of MOOs was analyzed by Western blot and immunofluorescence. RESULTS: MOOs can alleviate depressive-like behaviors in PSD rats. PSD rats showed increased expression of IL-18, IL-1ß, and NLRP3 inflammasome in the ischemic hippocampus, while MOOs reversed the elevation. NLRP3 downregulation ameliorated depressive-like behaviors and hippocampal inflammation response in PSD rats, while NLRP3 upregulation inhibited the effect of MOOs on depressive-like behaviors and hippocampal inflammation response in PSD rats. Moreover, we found that NLRP3 was mainly expressed on microglia. In vitro, MOOs effectively inhibited the expression of IL-18, IL-1ß, and NLRP3 inflammasome in LPS + ATP treated primary rat microglia. We also showed that modulation of NLRP3 inflammasome by MOOs was associated with the IκB/NF-κB p65 signaling pathway. CONCLUSION: Overall, our study reveals the antidepressive effect of MOOs on PSD rats through modulation of microglial NLRP3 inflammasome. We also provide a novel insight into hippocampal inflammation response in PSD pathology and put forward NLRP3 inflammasome as a potential therapeutic target for PSD.

Synergistic inflammatory signaling by cGAS may be involved in the development of atherosclerosis.

Inappropriate activation or overactivation of cyclic GMP-AMP synthase (cGAS) by double-stranded deoxyribonucleic acid (dsDNA) initiates a regulatory signaling cascade triggering a variety of inflammatory responses, which are a great threat to human health. This study focused on identifying the role of cGAS in atherosclerosis and its potential mechanisms. The relationship between cGAS and atherosclerosis was identified in an ApoE -/- mouse model. Meanwhile, RNA sequencing (RNA-seq) analysis of the underlying mechanisms of atherosclerosis in RAW264.7 macrophages treated with cGAS inhibition was conducted. Results showed that cGAS was positively correlated with atherosclerotic plaque area, and was mainly distributed in macrophages. RNA-seq analysis revealed that inflammatory response, immune response and cytokine-cytokine receptor interaction may play important roles in the development of atherosclerosis. Real-time quantitative polymerase chain reaction (RT-qPCR) results showed that the expression of the pro-inflammatory factors, signal transducer and activator of transcription (Stat), interferon regulatory factor (Irf), toll-like receptors (Tlrs), and type I interferons (Ifns) were synergistically reduced when cGAS was inhibited. Furthermore, cGAS inhibition significantly inhibited RAW264.7 macrophage M1 polarization. These results demonstrate that cGAS may contribute to the development of atherosclerosis through synergistic inflammatory signaling of TLRs, STAT/IRF as well as IFNs, leading to macrophage M1 polarization.

Postoperative Guillain-Barré Syndrome, a Neurologic Complication that Must Not Be Overlooked: A Literature Review.

BACKGROUND: Guillain-Barré syndrome (GBS) is an uncommon, yet life-threatening postoperative neuropathic complication that is easily neglected, and hence, timely treatment is not provided in the clinics. This review aims to summarize the clinical features of postoperative GBS, and thus, improve the understanding of postoperative GBS. METHODS: We reviewed the literature on postoperative GBS and assessed the demographic information, clinical manifestation, operation, time of onset of postoperative GBS, and prognosis. RESULTS: A total of 33 cases of postoperative GBS were included in this study. The average age of patients with postoperative GBS was 46.9 years, and there was a peak in occurrence of GBS between ages 50 and 70 years. Men seemed more likely to have postoperative GBS than did women, with a ratio of 2.67:1. Progressive muscular weakness, present in 31 of the cases, was the most common presentation. Patients with spinal surgery were at further increased risk for GBS, and 84.8% of the patients with GBS had a good prognosis after prompt treatment. CONCLUSIONS: Surgery is probably a potential risk factor for the occurrence of GBS. Early diagnosis and prompt treatment are imperative to reduce mortality.

Potential biomarkers for predicting hemorrhagic transformation of ischemic stroke.

Reperfusion therapy contributes to better clinical outcomes in patients with acute ischemic stroke but carries a more significant risk of hemorrhagic transformation (HT) compared to supportive care. Once HT occurs, the outcome is usually poor and this causes a dilemma in the treatment of ischemic stroke. Consequently, early prediction of HT would be extremely helpful for guiding precise treatment of ischemic stroke. In this review, we focus on summarizing biomarkers of HT and elucidating possible mechanisms so as to identify potential biomarkers for predicting HT.