Regulation of Toll-like receptor-mediated inflammatory response by microRNA-152-3p-mediated demethylation of MyD88 in systemic lupus erythematosus

Objective

microRNAs (miRNAs) play critical roles in embryogenesis, cell differentiation and the pathogenesis of several human diseases, including systemic lupus erythematosus (SLE). Toll-like receptors (TLRs) are also known to exert crucial functions in the immune response activation occurring in the pathogenesis of autoimmune diseases like SLE. Herein, the current study aimed to explore the potential role of miR-152-3p in TLR-mediated inflammatory response in SLE.

Methods

We determined the miR-152-3p expression profiles in CD4⁺ T cells and peripheral blood mononuclear cells (PBMCs) harvested from patients with SLE and healthy controls, and analyzed the correlation between miR-152-3p expression and clinicopathological parameters. CD70 and CD40L expression patterns in CD4⁺ T cells were assessed by RT-qPCR and flow cytometry. ChIP was adopted to determine the enrichment of DNA methyltransferase 1 (DNMT1) in the promoter region of myeloid differentiation factor 88 (MyD88).

Results

The obtained findings revealed that miR-152-3p was highly-expressed in CD4⁺ T cells and PBMCs of patients with SLE, and this high expression was associated with facial erythema, joint pain, double-stranded DNA, and IgG antibody. DNMT1 could be enriched in the MyD88 promoter, and miR-152-3p inhibited the methylation of MyD88 by targeting DNMT1. We also found that silencing miR-152-3p inhibited MyD88 expression not only to repress the autoreactivity of CD4⁺ T cells and but also to restrain their cellular inflammation, which were also validated in vivo.

Conclusion

Our study suggests that miR-152-3p promotes TLR-mediated inflammatory response in CD4⁺ T cells by regulating the DNMT1/MyD88 signaling pathway, which highlights novel anti-inflammatory target for SLE treatment.

     

氨甲环酸保守治疗慢性硬膜下血肿19例临床观察

目的：观察单独应用氨甲环酸保守治疗慢性硬膜下血肿的作用。方法对2014年3月至2015年8月西南医科大学附属医院住院治疗的19例慢性硬膜血肿患者,均经头颅 CT 检查确诊,给予静脉氨甲环酸（1 g／d）治疗,1周后改为口服（250 mg ,每日3次）,持续1～5个月[（2．73±1．05）个月],随访6～10个月。比较患者用药前后 CT 及临床症状变化。结果治疗效果分为有效和无效。19例中有效13例（68．4％）;无效6例（31．6％）,其中3例（15．8％）因临床症状加重改用手术治疗,1例（5．3％）因血肿量及症状变化不大改为手术治疗,1例（5．3％）因药物不良反应停药治疗,1例（5．3％）失访。结论单独应用氨甲环酸保守治疗慢性硬膜下血肿是安全有效。     

三维DSA彩色融合技术在大脑中动脉远端血管介入术中导航定位的应用

目的 评价三维DSA彩色融合技术在大脑中动脉远端血管介入术中导航定位的价值。方法 选取2018年6月至2020年12月在西南医科大学附属医院接受大脑中动脉远端动静脉畸形和动脉瘤介入治疗患者36例。随机将患者分为实验组（n=17,术中采用三维DSA彩色融合技术辅助导航）和对照组（n=19,采用二维路径图导航）。观察两组手术时间、术中微导管超选病变血管导引时间、X线透视时间、对比剂用量、辐射剂量[空气比释动能（AK）、剂量-面积乘积（DAP）]、手术相关并发症等情况。结果 实验组、对照组间手术时间[（95.80±12.50） min比（103.70±9.60） min]、微导管导引时间[（5.82±1.94） min比（8.47±2.48） min]、X线透视时间[（35.76±4.72） s比（51.16±5.80） s]、对比剂用量[（27.06±2.77） mL比（33.05±5.46） mL]、辐射剂量[AK:(88.48±21.67) mGy比（234.99±40.60） mGy,DAP:(7.11±1.07) Gyc/m2比（13.40±3.34） Gyc/m2,]差异有统计学...     

树脂吸附血液灌流器治疗肝性高胆红素血症的临床观察

目的　观察用丽珠HA型树脂吸附血液灌流器行血液灌流 (HP)治疗肝性高胆红素 (TBil≥ 171μmol/L)血症的疗效和安全性。 方法　选择肝性高胆红素血症患者 4 8例 ,观察血液灌流治疗前后的胆红素变化情况 ,评价灌流术的安全性。结果　血液灌流术后TBil较术前明显下降 ,经统计学处理有显著差异 (P <0 .0 1) ;血液灌流术不良反应发生率为 35 .4 % (主要是血压下降 2 0 .83% ,恶心 /呕吐 16 .6 7% )。结论　树脂吸附血液灌流器治疗肝性重度高胆红素血症有较满意疗效和较好安全性 ,可明显改善症状及缩短平均住院时间。     

TDO2 and tryptophan metabolites promote kynurenine/AhR signals to facilitate glioma progression and immunosuppression

Tumor cells exhibit enhanced uptake and processing of nutrients to fulfill the demands of rapid growth of tumor tissues. Tryptophan metabolizing dioxygenases are frequently up-regulated in several tumor types, which has been recognized as a crucial determinant in accelerated tumor progression. In our study, we explored the specific role of tryptophan 2,3-dioxygenase 2 (TDO2) in glioma progression. Analysis of mRNA profiles in 325 glioma patients based on the rich set of CCGA database was performed, which revealed that high TDO2 expression was tightly correlated with poor prognosis in glioma patients. TDO2 increased intracellular levels of tryptophan metabolism in the kynurenine (Kyn) pathway in vitro and in vivo, resulting in sustained glioma cell proliferation. Mechanistically, overexpression of TDO2 promoted the secretion of Kyn, which in turn stimulated the activation of the aryl hydrocarbon receptor (AhR)/AKT signaling pathway, resulting in heightened proliferative properties and tumorigenic potential in glioma cells. Meanwhile, Kyn produced by tumor cells further suppressed the proliferation of functional T cells, thereby resulting in immunosuppression and enhanced tumor growth in glioma. Our study showed that TDO2-induced increase in tryptophan metabolite Kyn played a pivotal role in glioma development via the AhR/AKT pro-survival signals and immunosuppressive effects, suggesting that the use of TDO2 inhibitors in combination with chemotherapy may be a novel strategy to effectively and synergistically eliminate glioma cells.     

染料木素和槲皮素体外抗肝纤维化作用

目的 研究染料木素和槲皮素对体外肝纤维化的保护作用。方法 细胞增殖和胶原合成分别用结晶紫染色法和3H-脯氨酸参入法。原胶原mRNA水平用RT-PCR法测定。结果 染料木素(25 ~ 70 mmolL-1)和槲皮素(6.25 ~ 50 mmolL-1)浓度依赖抑制PDGF促HSC-T6细胞增殖和TGFb1刺激的胶原合成及I型原胶原mRNA的表达。结论 染料木素和槲皮素抑制PDGF和TGFb1对星状细胞的作用可能对肝纤维化有保护作用。     

Onyx embolization of cavernous sinus dural arteriovenous fistulas via direct transorbital puncture under the guidance of three-dimensional reconstructed skull image (reports of six cases)

Backgrond

Because of complex angioarchitecture, the transarterial or venous pathway is not feasible for some cavernous sinus dural arteriovenous fistulas (CS DAVFs). We present six cases in which onyx embolization of a CS DAVFs was made possible through direct transorbital puncture.

Methods

In the present study, all patients were penetrated through one third of the medial-lateral of the inferior orbital rim under the guidance of fluoroscopy superimposed on the three-dimensional reconstructed skull image to complete embolization (onyx with or without coils). The records of patient demographics, clinical manifestation, fistula features, procedures, clinical outcome and angiographic outcome were reviewed and analyzed.

Results

In our series of six patients, the immediate angiographic result showed complete occlusion in all patients. The six patients experienced retrobulbarhematoma and eye swelling right after embolization, while the swelling significantly subsided after 3–5 days of conservative treatment. During the postoperative angiography and clinical follow-up (4–10 months), one of the patients had decreased visual acuity; the other five patients did not have neurological dysfunction.

Conclusions

Onyx embolization via direct transorbital puncture provides a method to be considered to treat CS DAVFs when the conventional transvenous approaches are inaccessible.     

蛋白激酶C抑制剂抑制白细胞介素1对骨细胞的作用

用富含成骨细胞的小鼠头颅骨细胞测试白细胞介素１（ＩＬ－１）对骨细胞的作用以及蛋白激酶Ｃ（ＰＫＣ）抑制剂Ｈ－７对ＩＬ－１作用的影响。结果表明ＩＬ－１（２５～１００Ｕ／ｍｌ）呈剂量依赖方式抑制骨细胞增殖和碱性磷酸酶活性；而对耐酒石酸酸性磷酸酶活性有增强作用。Ｈ－７（５～２０μｍｏｌ／Ｌ）对ＩＬ－１上述作用具有剂量依赖抑制作用。提示ＩＬ－１对骨细胞的作用可能与ＰＫＣ有关。