The inhibitory receptor CD300a is essential for neutrophil-mediated clearance of urinary tract infection in mice

Neutrophils play a crucial role in immune defense against and clearance of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection, the most common bacterial infection in healthy humans. CD300a is an inhibitory receptor that binds phosphatidylserine and phosphatidylethanolamine, presented on the membranes of apoptotic cells. CD300a binding to phosphatidylserine and phosphatidylethanolamine, also known as the “eat me” signal, mediates immune tolerance to dying cells. Here, we demonstrate for the first time that CD300a plays an important role in the neutrophil-mediated immune response to UPEC-induced urinary tract infection. We show that CD300a-deficient neutrophils have impaired phagocytic abilities and despite their increased accumulation at the site of infection, they are unable to reduce bacterial burden in the bladder, which results in significant exacerbation of infection and worse host outcome. Finally, we demonstrate that UPEC's pore forming toxin α-hemolysin induces upregulation of the CD300a ligand on infected bladder epithelial cells, signaling to neutrophils to be cleared.     

miR-183 promotes radioresistance of lung adenocarcinoma H1299 cells via epithelial-mesenchymal transition

Lung adenocarcinomas are usually sensitive to radiation therapy, but some develop resistance. Radiation resistance can lead to poor patient prognosis. Studies have shown that lung adenocarcinoma cells (H1299 cells) can develop radioresistance through epithelial-mesenchymal transition (EMT), and this process is regulated by miRNAs. However, it is unclear which miRNAs are involved in the process of EMT. In our present study, we found that miR-183 expression was increased in a radioresistant lung adenocarcinoma cell line (H1299R cells). We then explored the regulatory mechanism of miR-183 and found that it may be involved in the regulation of zinc finger E-box-binding homeobox 1 (ZEB1) expression and mediate EMT in lung adenocarcinoma cells. qPCR results showed that miR-183, ZEB1, and vimentin were highly expressed in H1299R cells, whereas no difference was observed in E-cadherin expression. Western blot results showed that ZEB1 and vimentin were highly expressed in H1299R cells, while E-cadherin expression was decreased. When miR-183 expression was inhibited in H1299R cells, radiation resistance, proliferation, and cell migration were decreased. The expression of ZEB1 and vimentin in H1299R cells was decreased, while the expression of E-cadherin was increased. Moreover, miR-183 overexpression in H1299 cells enhanced radiation resistance, proliferative capacity, and cell migration ability. The expression of ZEB1 and vimentin in H1299 cells was increased, while that of E-cadherin was decreased. In conclusion, miR-183 may promote EMT and radioresistance in H1299 cells, and targeting the miR-183-ZEB1 signaling pathway may be a promising approach for lung cancer treatment.     

Optimistic amnesia: how online and offline processing shape belief updating and memory biases in immediate and long-term optimism biases

When people are confronted with feedback that counters their prior beliefs, they preferentially rely on desirable rather than undesirable feedback in belief updating, i.e. an optimism bias. In two pre-registered EEG studies employing an adverse life event probability estimation task, we investigated the neurocognitive processes that support the formation and the change of optimism biases in immediate and 24 h delayed tests. We found that optimistic belief updating biases not only emerged immediately but also became significantly larger after 24 h, suggesting an active role of valence-dependent offline consolidation processes in the change of optimism biases. Participants also showed optimistic memory biases: they were less accurate in remembering undesirable than desirable feedback probabilities, with inferior memories of undesirable feedback associated with lower belief updating in the delayed test. Examining event-related brain potentials (ERPs) revealed that desirability of feedback biased initial encoding: desirable feedback elicited larger P300s than undesirable feedback, with larger P300 amplitudes predicting both higher belief updating and memory accuracies. These results suggest that desirability of feedback could bias both online and offline memory-related processes such as encoding and consolidation, with both processes contributing to the formation and change of optimism biases.     

Connecting the P300 to the diagnosis and prognosis of unconscious patients

The residual consciousness of unconscious patients can be detected by studying the P300, a wave among event-related potentials. Previous studies have applied tones, the subject's name and other names as stimuli. However, the results were not satisfactory. In this study, we changed the constituent order of subjects' two-character names to create derived names. The subject's derived names, together with tones and their own names, were used as auditory stimuli in event-related potential experiments. Healthy controls and unconscious patients were included in this study and made to listen to these auditory stimuli. In the two paradigms, a sine tone followed by the subject's own name and the subject's derived name followed by the subject's own name were used as standard and deviant stimuli, respectively. The results showed that all healthy controls had the P300 using both paradigms, and that the P300 in the second paradigm had a longer latency and two peaks. All minimally conscious state patients had the P300 in the first paradigm and the majority of them had the P300 in the second paradigm. Most vegetative state patients had no P300. Patients who showed the P300 in the two paradigms had more residual consciousness, and patients with the two-peak P300 had a higher probability of awakening within a short time. Our experimental findings suggest that the P300 event-related potential could reflect the conscious state of unconscious patients.     

接受式音乐治疗对精神分裂症患者认知功能的影响

目的：探讨接受式音乐治疗对精神分裂症患者认知功能的影响。方法将58例精神分裂症患者随机分为两组,均接受阿立哌唑治疗,研究组联合接受式音乐治疗,观察8周。选取29名健康者设为健康组。研究组及对照组于治疗前后采用简明精神病量表评定临床疗效,并进行P300检测;健康组于入组时进行P300检测。结果治疗8周末研究组和对照组简明精神病量表评分均较治疗前显著降低（P＜0．01）,研究组显著低于对照组（P＜0．01）;研究组显效率及总有效率高于对照组,但差异无显著性（ P＞0．05）。治疗前研究组和对照组P300潜伏期较健康组显著延长（ P＜0．01）,波幅较健康组显著降低（ P＜0．01）;治疗8周末,研究组和对照组 P300潜伏期较治疗前显著缩短（P＜0．05或0．01）,研究组波幅较治疗前显著升高（P＜0．05）,对照组则无显著变化（P＞0．05）,与健康组比较差异无显著性（P＞0．05）。结论接受式音乐治疗对改善精神分裂症患者认知功能具有增效作用。     

miR－21调控TGF－β1诱导的大鼠BMSCs向肌成纤维细胞分化的机制研究

目的：在细胞水平探索miR－21在调控TGF－β1诱导的大鼠骨髓间充质干细胞向肌成纤维细胞分化中的作用。方法：全髓培养法培养原代大鼠骨髓间充质干细胞,培养至第三代时用TGF－β1分组诱导培养,检测TGF－β1对大鼠BMSCs促纤维化的作用及该过程中不同浓度梯度TGF－β1诱导以及不同时间段miR－21的表达变化;通过转染miR－21 mimics（高表达）不同时间点检测其对α－SMA表达的影响。结果：TGF－β1能促进大鼠骨髓间充质干细胞向成纤维,肌成纤维细胞分化;大鼠骨髓间充质干细胞向成纤维,肌成纤维细胞分化后miR－21表达上调;上调miR－21能促进大鼠BMSCs的纤维化作用。结论：miR－21 mimics能够促进大鼠BMSCs的纤维化作用。     

Decreased expression of microRNA-130a correlates with TNF-α in the development of osteoarthritis

Objective: Increased expression of tumor necrosis factor a (TNF-α) has emerged as an important inflammatory factor in osteoarthritis (OA) and other joint diseases. The study was performed to investigate whether the expression of TNF-α in human chondrocytes was regulated by miRNAs. Methods: MiRNA-130a and TNF-α expression in cartilage specimens was examined in patients with knee osteoarthritis, chondrocytes and osteoarthritis rat model. Chondrocytes were transfected with siRNAs as a gene silencing methods. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Results: Increased TNF-α and decreased miRNA-130a were observed in tissues from osteoarthritis patients. Moreover, we found a highly negitive correlation between miRNA-130a and TNF-α. Next, miRNA-130a loss-of-function increased the expression of TNF-α and promoted inflammation in chondrocytes. It was reasonable that miRNA-130a regulated a distinct underlying molecular and pathogenic mechanism of OA by forming a negative feedback loop with TNF-α. Furthermore, there were the abnormalities of bone metabolism in OA rat, which showed the miRNA-130a and TNF-α dysfunction that was one of important factors for the occurrence and development of OA. Conclusions: Our results indicated that miR-130a played an important role in regulating the expression of TNF-α in human chondrocytes and identified miR-130a as a novel therapeutic target in OA.     

基于微流控平台的胶质母细胞瘤干细胞中miRNA-874表达的研究

目的通过微流控检测平台,研究miRNA-874（miR-874）表达在胶质母细胞瘤干细胞（GSCs）生长中的作用及意义。 方法应用高通量、多样本、低成本的微流控技术,对GSCs和神经干细胞（NSCs）进行miR-874转染,并通过荧光定量PCR检测细胞内miR-874和mRNA表达等一系列细胞分子生物实验,研究miRNA-874对GSCs生长和凋亡的作用。 结果miR-874在GSCs中的表达显著降低,约为NSCs中表达量的2%~40%（P<0.05）。利用树状分子将miR-874转染入GSCs中后,GSCs的细胞数量显著下降,凋亡细胞的数量显著上升,提示miR-874对GSCs具有杀伤作用。 结论miR-874在GSCs中表达显著降低,在GSCs中过表达miR-874会导致显著的细胞生长抑制和死亡,有助于开发基于miRNA的新型脑癌药物和疗法。     

miRNA-212在乳腺癌的表达及其与临床病理特征的关系

目的分析miRNA-212在乳腺癌中的表达及其与临床病理特征的关系。方法选择90例乳腺癌患者的手术标本(癌组织及其癌旁组织)提取总RNA,采用TaqMan探针逆转、实时定量PCR检测miRNA-212在乳腺癌及其癌旁正常组织中的表达量,并分析其与临床病理特征关系。结果乳腺癌组织miRNA-212表达量为3.06(0.146-10.274),与癌旁正常组织相比显著上调;miRNA-212的表达与TNM分期相关,TNM分期越高,miRNA-212表达越高;miRNA-212的表达也与淋巴结转移相关,淋巴结转移患者miRNA-212表达增加。结论miRNA-212表达上调可能与乳腺癌的发生及其转移有关。     

盐酸文拉法辛缓释片对42例Ⅱ型精神分裂症患者听觉P300的影响

目的：应用事件相关电位（ERP）听觉P300（即P3）评估盐酸文拉法辛缓释片对Ⅱ型精神分裂症患者认知功能的影响。方法：选取疗效已达显著进步以上的Ⅱ型精神分裂症患者42例,随机分为研究组（22例）和对照组（20例）。研究组给予盐酸文拉法辛缓释片治疗,在治疗前后对两组患者分别进行听觉ERP检查及阳性症状与阴性症状量表（PANss）评定。结果：在治疗后,研究组靶刺激P300潜伏期缩短（P〈0．05）和波幅升高（P〈0．05）,PANSS评定提示阴性因子分、反应缺乏因子分及抑郁因子分下降和激活因子分升高（P〈0．05）,与对照组比较,差异有统计学意义（P〈0．05）。对照组在治疗前后P300各项目和PANSS评分比较差异无统计学意义（P〉0．05）。结论：从ERP的P300可反映出盐酸文拉法辛缓释片能改善U型精神分裂症患者的认知功能。