Low-dose LPS alleviates early brain injury after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.

BACKGROUND: Low-dose lipopolysaccharide (LPS) protects against early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanism underlying the neuroprotective roles of low-dose LPS remain largely undefined. METHODS: A SAH mice model was established and the pathological changes of brain were evaluated by wet-dry weight method, HE and Nissl staining, and blood-brain barrier (BBB) permeability assay. Cell apoptosis and inflammation were monitored by TUNEL, flow cytometry and ELISA assays. qRT-PCR, immunofluorescence and Western blot were used to detect the expression of microglial polarization-related or oxidative stress-associated markers. Bioinformatics analysis, luciferase and ChIP assays were employed to detect the direct association between FOXO1 and IL-10 promoter. The ubiquitination of FOXO1 in the in vitro SAH model was detected by co-IP. RESULTS: Low-dose LPS alleviated SAH-induced neurological dysfunction, brain edema, BBB disruption, damage in the hippocampus, neuronal apoptosis and inflammation via modulating microglial M1/M2 polarization by IL-10/IL-10R1 signaling. Mechanistic studies showed that FOXO1 acted as a transcriptional activator of IL-10. USP19 mediated the deubiquitination of FOXO1 to activate IL-10/IL-10R1 signaling, thereby regulating microglial M1/M2 polarization. Functional experiments revealed that low-dose LPS upregulated USP19 to modulate microglial M1/M2 polarization via FOXO1/IL-10/IL-10R1 signaling in SAH mice. CONCLUSION: Low-dose LPS protected against EBI after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.

Research progress on moyamoya disease combined with thyroid diseases.

Moyamoya disease (MMD), also known as abnormal cerebral vascular network disease, is characterized by progressive occlusion or stenosis of the internal carotid and cerebral arteries, as well as the formation of an abnormal cerebral vascular network. It can occur anywhere in the world but is most common in China, Japan, and the Republic of Korea. In recent years, there have been increasing reports on the coexistence of thyroid diseases and MMD, but the mechanism of their coexistence is still unclear. For this article, we used keywords such as "moyamoya disease", "thyroid", "Grave disease", "thyrotoxicosis", and "thyroid autoimmune antibodies" to search for 52 articles that met the requirements in medical databases such as PubMed and Web of Science. This article also reviews the research on the role of thyroid hormone, the mechanism of immune antibodies, the possible correlation between thyroid diseases and MMD disease genes, and the treatment methods, and discusses the possible relationship between MMD and thyroid diseases to provide a reference for the pathogenesis and treatment of MMD with thyroid diseases.

Clinical value of the systemic immune-inflammation index in moyamoya disease.

Background: Moyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. The underlying pathophysiological mechanism of moyamoya disease remains to be elucidated, but recent studies have increasingly highlighted that abnormal immune response may be a potential trigger for MMD. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are inflammatory markers that can reflect the immune-inflammation state of the disease. Objective: The purpose of this study was to investigate SII, NLR, and PLR in patients with moyamoya disease. Methods: A total of 154 patients with moyamoya disease (MMD group) and 321 age- and sex-matched healthy subjects (control group) were included in this retrospective case-control study. Complete blood count parameters were assayed to calculate the SII, NLR, and PLR values. Results: The SII, NLR, and PLR values in the moyamoya disease group were significantly higher than those in the control group [754 ± 499 vs. 411 ± 205 (P < 0.001), 2.83 ± 1.98 vs. 1.81 ± 0.72 (P < 0.001), and 152 ± 64 vs. 120 ± 42 (P < 0.001), respectively]. The SII in the medium-moyamoya vessels of moyamoya disease was higher than that in the high-moyamoya vessels and low-moyamoya vessels (P = 0.005). Using the receiver operating characteristic (ROC) curve analysis to predict MMD, the highest area under the curve (AUC) was determined for SII (0.76 for SII, 0.69 for NLR, and 0.66 for PLR). Conclusion: Based on the results of this study, patients with moyamoya disease admitted for inpatient care due to acute or chronic stroke have significantly higher SII, NLR, and PLR when compared to blood samples drawn from completely healthy controls in a non-emergent outpatient setting. While the findings may suggest that inflammation plays a role in moyamoya disease, further studies are warranted to corroborate such an association. In the middle stage of moyamoya disease, there may be a more intense imbalance of immune inflammation. Further studies are needed to determine whether the SII index contributes to the diagnosis or serves as a potential marker of an inflammatory response in patients with moyamoya disease.

[The relationship of blood glucose and the expression of insulin-like growth factor-1 receptor mRNA in diabetic cardiomyopathy: a preliminary study with rats].

OBJECTIVE: To investigate the role of insulin-like growth factor-1 receptor mRNA (IGF-1R mRNA) in diabetic cardiomyopathy. METHODS: Alloxan of the doses of 150 and 200 mg/kg was injected intraperitoneally into 20 male Wistar rats respectively so as to establish type 1 diabetes mellitus models (Groups B and C). The rats were used as normal controls (Groups A). Three months later the rats were killed and blood samples were collected to undergo examination of plasma glucose, insulin, glycated hemoglobin (HbA1c), and C peptide. The hearts were taken out to undergo light and transmission electron microscopy and in situ hybridization to detect the expression of IGF-1R mRNA in the myocardium. RESULTS: The levels of plasma glucose, HbA1c, insulin and C peptide of Groups B and C were all significantly higher than those of Group A (all P < 0.01), and the levels of plasma glucose, HbA1c, insulin and C peptide of Group C being significantly higher than those of Group B too (all P < 0.01). Expression of IGF-1R mRNA was found in the myocardium of Groups A, B and C with the distribution areas of 20%, 30%, and 38% respectively. The expression of IGF-1R mRNA in myocardium was positively correlated with blood glucose and HbA1c (r = 0.869, 0.865, both P < 0.01). CONCLUSION: The increased expression of IGF-1R mRNA in the myocardium may play an important role in the progression of diabetic cardiomyopathy.

[Observation on specificity of acupuncture location in treatment of acute apoplexy by scalp penetration needling].

OBJECTIVE: To observe the clinical effects of scalp penetration acupuncture and conventional scalp acupuncture for treatment of acute apoplexy, to seek the effective location and mechanism of scalp acupuncture treatment for acute apoplexy. METHODS: Sixty cases of the apoplexy were randomly divided into an observation group and a control group, 30 cases in each group. Basis on the neurological treatment, the observation group was treated with penetration needling through Baihui (GV 20) to Taiyang (EX-HN 5) on the affected side, with four needles relay; the control group was treated with penetration needling at anterior oblique line of parietotemporal region, with four needles relay. After 14 days of treatment, the neurological deficit scores (NDS) and the therapeutic effects were compared before and after treatment, and the contents of plasma endothelins (ET) and the calcitonin gene-related peptide (CGRP) were tested respectively on the 2nd and 14th day after treatment. RESULTS: The effective rate of 86.7% (26/30) in the observation group was superior to that of 80.0% (24/30) in the control group; the NDS of both groups were obviously decreased after treatment (both P < 0.01), the improvement degree in the observation group was better than that of the control group (P < 0.01); the ET level was obviously decreased and the CGRP level was obviously increased in both groups after treatment (all P < 0.01), and the range of change was more significant in the observation group (P < 0.01). CONCLUSION: Penetration needling through Baihui (GV 20) to Taiyang (EX-HN 5) is an effective treatment for acute apoplexy, which is better than conventional scalp acupuncture.