Interactions between immune response to fungal infection and microRNAs: The pioneer tuners

Due to their physiological and biological characteristics, numerous fungi are potentially emerging pathogens. Active dynamicity of fungal pathogens causes life-threatening infections annually impose high costs to the health systems. Although immune responses play crucial roles in controlling the fate of fungal infections, immunocompromised patients are at high risk with high mortality. Tuning the immune response against fungal infections might be an effective strategy for controlling and reducing the pathological damages. MicroRNAs (miRNAs) are known as the master regulators of immune response. These single-stranded tuners (18-23 bp non-coding RNAs) are endogenously expressed by all metazoan eukaryotes and have emerged as the master gene expression controllers of at least 30% human genes. In this review article, following the review of biology and physiology (biogenesis and mechanism of actions) of miRNAs and immune response against fungal infections, the interactions between them were scrutinised. In conclusion, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. Undoubtedly, advanced studies in this field, further identifying of miRNA roles in governing the immune response, pave the way for inclusion of miRNA-related immunotherapeutic in the treatment of life-threatening fungal infections.     

调衡方对Lewis肺癌荷瘤体巨噬细胞吞噬功能的影响＊

目的 研究调衡方对Lewis肺癌荷瘤小鼠巨噬细胞形态、 数量及活性的影响，探讨调衡方对荷瘤体巨噬细胞作用的免疫调节机制。方法 将传代培养的Lewis肺癌细胞接种于小鼠右腋皮下建转移肺癌模型；灌胃给药8 d后，从小鼠腹腔分离抽取巨噬细胞并培养；调衡方各组巨噬细胞培养48 h后，在显微镜下观察活细胞的形态，墨汁吞噬试验以及金葡菌吞噬试验观察巨噬细胞的吞噬能力，细胞酶化学染色观察巨噬细胞胞内酸性磷酸酶的变化，用酶联免疫吸附法（ELISA）检测各培养组M?上清中IL-1、IL-6、TNF-α表达水平。结果 调衡方小、中、大剂量各组巨噬细胞培养48 h后，与对照组比较，巨噬细胞体积显著增大，对墨汁和金葡菌的吞噬能力均显著提升，酸性磷酸酶的活性也明显增强，且能抑制炎性因子IL-1、IL-6、TNF-α分泌，这均与给药浓度呈正相关。结论 调衡方能增强巨噬细胞的吞噬功能，进而提高胞内酸性磷酸酶等的活性，通过抑制巨噬细胞分泌炎性因子（IL-1、IL-6、TNF-α）有控制巨噬细胞向M2型极化的可能，并减轻肿瘤浸润程度，降低肿瘤发展及转移，而发挥抗肿瘤免疫调节的作用。     

胡蜂毒提取物对胶原诱导性类风湿性关节炎大鼠的作用研究

目的建立胶原诱导性类风湿关节炎(collagen-induced arthritis,CIA)大鼠模型来探讨胡蜂毒提取物对大鼠类风湿性关节炎(rheumatoid arthritis,RA)的治疗作用。方法将SD大鼠随机分为正常组、模型组、阳性对照组(注射用蜂毒冻干粉,1.25 mg·kg^-1)和胡蜂毒提取物低、中、高剂量(0.125、0.25、0.5 mg·kg^-1)组,除正常组外,其余各组采用多点注射鸡Ⅱ型胶原加完全弗氏佐剂的方法来诱导大鼠RA模型,每7 d一次,共14 d。造模结束后,各给药组于足趾皮下注射对应剂量的药物,连续给药14 d。分别于造模前、造模第14天和给药第14天测量大鼠踝关节直径和周长,并进行AI评分;观察大鼠脏器指数和踝关节组织HE染色的变化;采用酶联免疫吸附测定(ELISA)检测大鼠血清中相关炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、IL-8、前列腺素(PG)E-2、环氧化酶(COX)-2和类风湿因子免疫球蛋白(Ig)G、Ig A、Ig M的含量变化;利用流式细胞术检测大鼠脾脏T细胞亚群的变化。结果与模型组比较,胡蜂毒提取物对CIΑ大鼠的关节肿胀(直径及周长)抑制效果显著(P<0.01),能明显降低其AI评分(P<0.01或P<0.05),能不同程度恢复大鼠的脏器指数(P<0.01或P<0.05),改善踝关节组织病理学结构病变,降低大鼠血清中各炎症因子和类风湿因子的表达(P<0.01或P<0.05),调节和改善T细胞亚群比例的紊乱(P<0.01或P<0.05)。结论胡蜂毒提取物对CIA大鼠具有较好的治疗作用,这与其对炎症细胞因子网络的调控和对免疫的调节有关系。     

KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer

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Can a pragmatic responsive feeding scale be developed and applied globally?

Responsive feeding (RF) has been recognized as necessary to prevent all forms of malnutrition including stunting and childhood obesity. Specific RF guidelines have been developed, but it is unclear how RF behaviours can be monitored systematically. Therefore, developing valid and reliable abbreviated and pragmatic RF scales is an important global priority. This is challenging, as RF is a construct with multiple dimensions including recognizing and responding to hunger and satiety cues, providing a nurturing environment during feeding episodes, and understanding how feeding needs evolve as a function of the developmental stage of the young child. Further, RF is embedded within the responsive parenting framework that in addition to RF includes sleep, soothing and play routines and the interconnections between them. A recent pioneer study conducted in a rural area of Cambodia validated an 8‐item RF scale through direct feeding observations of 6‐ to 23‐month‐old infants at home, as part of two cross‐sectional surveys conducted before and after a complementary feeding intervention. It is important for similar research to be conducted elsewhere to find out if it is possible or not to develop a core RF scale that is valid and reliable and that has adequate specificity and sensitivity for application in community studies and population surveys globally. As highlighted in this article, different definitions of RF have been used in the field; thus, it is important to reach consensus on a single definition to help move this research area forward.     

MicroRNA-181c provides neuroprotection in an intracerebral hemorrhage model

Apoptosis is an important factor during the early stage of intracerebral hemorrhage.MiR-181 c plays a key regulatory role in apoptosis.However,whether miR-181 c is involved in apoptosis of prophase cells after intracerebral hemorrhage remains unclear.Therefore,in vitro and in vivo experiments were conducted to test this hypothesis.In vivo experiments:collagenase type VII was injected into the basal ganglia of adult Sprague-Dawley rats to establish an intracerebral hemorrhage model.MiR-181 c mimic or inhibitor was injected in situ 4 hours after intracerebral hemorrhage.Neurological functional defects(neurological severity scores)were assessed 1,7,and 14 days after model establishment.Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and western blot assay were conducted 14 days after model establishment.In vitro experiments:PC12 cells were cultured under oxygen-glucose deprivation,and hemins were added to simulate intracerebral hemorrhage in vitro.MiR-181 c mimic or inhibitor was added to regulate miR-181 c expression.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,luciferase reporter system,and western blot assay were performed.Experimental results revealed differences in miR-181 c expression in brain tissues of both patients and rats with cerebral hemorrhage.In addition,in vitro experiments found that miR-181 c overexpression could upregulate the Bcl-2/Bax ratio to inhibit apoptosis,while inhibition of miR-181 c expression could reduce the Bcl-2/Bax ratio and aggravate apoptosis of cells.Regulation of apoptosis occurred through the phosphoinositide 3 kinase(PI3 K)/Akt pathway by targeting of phosphatase and tensin homolog deleted on chromosome ten(PTEN).Higher miR-181 c overexpression correlated with lower neurological severity scores,indicating better recovery of neurological function.In conclusion,miR-181 c affects the prognosis of intracerebral hemorrhage by regulating apoptosis,and these effects might be directly mediated and regulated by targeting of the PTEN\PI3 K/Akt pathway and Bcl-2/Bax ratio.Furthermore,these results indicated that miR-181 c played a neuroprotective role in intracerebral hemorrhage by regulating apoptosis of nerve cells,thus providing a potential target for the prevention and treatment of intracerebral hemorrhage.Testing of human serum was authorized by the Ethics Committee of China Medical University(No.2012-38-1)on February 20,2012.The protocol was registered with the Chinese Clinical Trial Registry(Registration No.ChiCTR-COC-17013559).The animal study was approved by the Institutional Animal Care and Use Committee of China Medical University(approval No.2017008)on March 8,2017.     

Predictors of psychological distress amongst nursing students: A multicenter cross-sectional study

Undergraduate nursing students show high-stress levels. In students, stress has been linked to adverse physical and psychological health outcomes and academic and clinical demands. To date, there are few studies dealing with psychological predictors of stress amongst nursing students. This study aimed to assess psychological distress in a sample of Italian nursing students and to explore its relationship with sociodemographic and psychological factors, specifically dispositional mindfulness, emotional regulation difficulties, and empathy. A multicenter cross-sectional survey design was employed. Participants were recruited from five teaching hospitals associated with a public university in northern Italy. A sample of 622 undergraduate nursing students was recruited. Participants were recruited on campus and completed a paper-and-pencil survey. More than 70% of nursing students reported meaningful levels of psychological distress. Students with higher dispositional mindfulness scores had lower psychological distress, whereas emotional regulation difficulties and empathic personal distress were positively associated with perceived stress. No gender differences were found in stress levels, but senior students showed lower psychological distress than more junior students. Interventions aimed at increasing mindfulness facets and improving emotional regulation strategies may help to reduce perceived psychological stress in nursing students.     

基于动态优化算法的复杂生物网络的状态调控

近年研究表明,某些药物能改变基因调控网络(GRNs)中的调控反应参数,促使细胞从病变状态转移到正常状态。在此基础上,有学者构建了基于吸引子和分岔理论的状态调控框架。现有的控制策略中,控制信号规律都是自行拟定的,并且所使用的参数扰动法仅能求出单控制变量情况下状态转移所需的时间。因此,针对以非线性常微分方程组(ODEs)形式描述的复杂生物网络,本文提出了一种基于动态优化算法改变网络状态的最优调控方法,在掌握生物网络基本特性的基础上建立了动态优化问题,并以简单低维的三节点GRN和复杂高维的癌症GRN为例,利用MATLAB计算得到单控制变量及多控制变量条件下的最优控制策略。本文所提方法旨在实现精确且快速的状态调控,为试验研究和实际治疗提供参考依据。     

Prefrontal modulation of frustration-related physiology in preschool children ranging from low to severe irritability

Limbic-prefrontal connectivity during negative emotional challenges underpins a wide range of psychiatric disorders, yet the early development of this system is largely unknown due to difficulties imaging young children. Functional Near-Infrared Spectroscopy (fNIRS) has advanced an understanding of early emotion-related prefrontal activation and psychopathology, but cannot detect activation below the outer cortex. Galvanic skin response (GSR) is a sensitive index of autonomic arousal strongly influenced by numerous limbic structures. We recorded simultaneous lateral prefrontal cortex (lPFC) activation via fNIRS and GSR in 73 3- to 5-year-old children, who ranged from low to severe levels of irritability, during a frustration task. The goal of the study was to test how frustration-related PFC activation modulated psychophysiology in preschool children, and whether associations were moderated by irritability severity. Results showed lPFC activation significantly increased, and GSR levels significantly decreased, as children moved from frustration to rest, such that preschoolers with the highest activation had the steepest recovery. Further, this relation was moderated by irritability such that children with severe irritability showed no association between lPFC activation and GSR. Results suggest functional connections between prefrontal and autonomic nervous systems are in place early in life, with evidence of lPFC down-regulation of frustration-based stress that is altered in early psychopathology. Combining fNIRS and GSR may be a promising novel approach for inferring limbic-PFC processes that drive early emotion regulation and psychopathology.