Mmu-miR-92a-2-5p targets TLR2 to relieve Schistosoma japonicum-induced liver fibrosis

According to conservative estimates, >230 million people are infected with schistosomiasis,which becomes one of the most common parasitic diseases. This study focuses on investigating in vivo and in vitro effects of mmu-miR-92a-2-5p in Schistosoma japonicum-induced liver fibrosis by targeting TLR2. Through bioinformatic analysis, the overexpression of TLR2 and the down-regulation of mmu-miR-92a-2-5p were revealed in the progression of S. japonicum-induced liver fibrosis. BALB/C mice were taken advantage to construct normal control and schistosomiasis liver fibrosis (SLF) model. The mice in model groups were transfected recombinant lentivirus (Lenti-mmu-miR-92a-2-5p or Lenti-NC) to alter the expression of mmu-miR-92a-2-5p in vivo. HE and Masson staining were employed to observe the pathological changes and collagenous fibrosis. QRT-PCR showed that mmu-miR-92a-2-5p was decreased while TLR2 was elevated in the infected groups. However, lenti-mmu-miR-92a-2-5p group could inhibit liver fibrosis. Then the effect of mmu-miR-92a-2-5p on S. japonicum-induced liver fibrosis including cell apoptosis rates, proliferation and proteins related to liver fibrosis was examined in NIH-3T3 mouse embryonic fibroblasts. Moreover, the association between mmu-miR-92a-2-5p and TLR2 was detected by dual-luciferase reporter gene assay and the expression of cytokines IL-4, IFN-γ and TNF-α in SLF model was detected by ELISA. Further, the knockout of TLR2 in C57BL/6J mice was used to confirm the association between mmu-miR-92a-2-5p and TLR2. Thus, these findings demonstrated that mmu-miR-92a-2-5p inhibited S. japonicum-induced liver fibrosis by targeting TLR2 in vitro and in vivo.     

Adverse childhood experiences,inflammation, and depressive symptoms in later life: a prospective cohort study

BackgroundExposure to adverse childhood experiences (ACEs) has been associated with both inflammation and depression. However, little research has examined the potential mediational role of inflammation in the link between ACEs and depression using longitudinal data. Therefore, we investigated the direct and indirect effects of ACEs on inflammation, depression, and their change trajectories over time.MethodsWe used data from the English Longitudinal Study of Ageing. Four ACE categories were assessed retrospectively at wave 3 (2006–07): abuse (physical or sexual abuse or physical assault), family dysfunction (parent arguments, parent mental illness or substance abuse, or parent separation or divorce), poor parent–child bonding (maternal or paternal), and loss of an attachment figure (separation from mother for >6 months, parent death, foster care or adoption, or institutionalisation). A cumulative ACE score was calculated representing the total number of ACEs experienced by the participants. Concentration of C-reactive protein (CRP), an inflammatory marker, was measured at waves 2 (2004–05), 4 (2008–09), and 6 (2012–13). Depressive symptoms were ascertained using the 8-item Centre for Epidemiological Studies Depression Scale from waves 6 to 8 (2016–17). The longitudinal direct and indirect effects of ACEs were estimated using parallel process latent growth curve modelling. All analyses were adjusted for relevant confounders. Missing data were estimated using multiple imputation.ResultsAmong the study sample (N=4382; mean age 70 years; 56% female), 24% of participants reported one ACE and 13% had two or three ACEs. The percentage of participants with three or more depressive symptoms was 21% at baseline. Greater cumulative exposure to ACEs was associated with increased CRP concentration (β=0·042, p=0·010) and depressive symptoms (β=0·164, p<0·0001) at baseline and predicted a steeper increase in these outcomes throughout the study (β_CRP=0·074, p=0·011; β_Depression=0·338, p<0·0001). However, indirect effects of ACEs on depression mediated by CRP were not observed, with only weak associations between CRP and depressive symptoms (β_iDepression=0·032, p=0·173; β_sDepression=0·067, p=0·240). Sensitivity analyses using only somatic depressive symptoms as the outcome revealed a positive association between CRP and somatic symptoms at baseline (β_iDepression=0·068, p=0·008), although the indirect effects remained non-significant in this model.InterpretationBiological mechanisms other than inflammation might underlie the relationship between ACEs and depression. Psychosocial interventions to reduce the negative effects of ACEs on children's development could help to reduce the risk of depression and of other medical conditions linked to inflammation.FundingEconomic and Social Research Council–Biotechnology and Biological Sciences Research Council Soc-B Centre for Doctoral Training (ES/P000347/1).     

蛤蚧皮质加厚区的形态解剖及三维重建

目的明确蛤蚧皮质加厚区的位置、核团的形态及与比邻结构的关系,为研究皮质加厚区的功能提供依据。方法对蛤蚧脑行冷冻冠状连续切片(厚60μm),Nissl染色,对每张含有皮质加厚区的切片进行摄片和测量,选取其中1套用于三维重建,重组软件为3D MAX。结果1.皮质加厚区位于端脑吻侧端,前背侧室嵴外侧,外侧皮层内侧和背侧皮层腹侧。皮质加厚区的吻尾长(912.67±110.96)μm(n=10),体积(0.1430±0.0414)μm3(n=10)。2.皮质加厚区从吻侧端到尾侧端大约可分为前段、中段、后段和末段。后段的背腹径最长,可分为背侧部和腹侧部,两部分的细胞分界清晰。结论皮质加厚区为一吻尾径长于内外径的狭长片状结构,背侧缘较腹侧缘平滑;加厚区的尾侧端比吻侧端大,且尾端的后段分离成背侧和腹侧两个细胞群。     

Potential protection of vitamin C against liver-lesioned mice

Pathologically, liver injury can result from sustained trauma to hepatocytes, including acute damage. Thus, attenuation of hepatocellular lesion may help improve liver functions. The purpose of this study was to explore the potential advantages of vitamin C (VC) intake on acutely intralesional liver in carbon tetrachloride (CCl₄)-exposed mice. Here our data showed that VC supplementation contributed to ameliorated vital signs of CCl₄-lesioned mice, resulting in dose-dependent reduction of hepatomegaly. VC lowered the levels of liver functional enzymes including alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) in serum, while concentration of lactic acid concentration in blood plasma was decreased. VC-administered CCl₄-lesioned mice manifested increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-P_X), while the malondialdehyde (MDA) content was reduced in liver tissue. Moreover, VC consumption attenuated hepatotoxic injuries of CCl₄-lesioned mice, in which the number of TNF-α positive cells was dose-dependently reduced. Furthermore, intrahepatic expression of TRL-4 mRNA, a vital inflammation-regulator, was down-regulated in VC-administered mice. Overall, we conclude that VC has the potentiality of anti-hepatotoxicity that is capable of ameliorating liver functions, speculating that therapeutic mechanism relates to normalizing metabolism and blocking inflammatory stress in the liver.     

Do certain signal transduction mechanisms explain the comorbidity of epilepsy and mood disorders?

It is well known that mood disorders are highly prevalent in patients with epilepsy. Although several studies have aimed to characterize alterations in different types of receptors associated with both disturbances, there is a lack of studies focused on identifying the causes of this comorbidity. Here, we described some changes at the biochemical level involving serotonin, dopamine, and γ-aminobutyric acid (GABA) receptors as well as signal transduction mechanisms that may explain the coexistence of both epilepsy and mood disorders. Finally, the identification of common pathophysiological mechanisms associated with receptor–receptor interaction (heterodimers) could allow designing new strategies for treatment of patients with epilepsy and comorbid mood disorders.This article is part of a Special Issue entitled “NEWroscience 2013”.     

医学物理界科研滞后原因探讨

研究目的在于推动医学物理界科研发展。通过对医学物理界历史和现实的科研状况回顾与分析，揭示影响医学物理界开展科研的主要原因：缺乏科研带头人的传帮带，缺乏科研设备，教师的科研要求太低动力不足，知识面太窄，没有明确的研究方向。强调指出科研能否开展起来，贡献大小关键在于主观能动性的发挥，在端正科研态度的基础上，应遵循“一综述、二对比、三确定”的三个步骤，认真选定有发展前景的研究方向，掌握研究该方向课题的相关理论和技能；最后部分阐明了选题常用的四种方法：（1）顺藤摸瓜找题，（2）到相关社会实践中找题，（3）阅读文献找题，（4）学术交流找题。     

临床血液流变学指标检测报告单设计不合理应该修正

笔者发现虽然血液流变学广泛用于l临床已经20几年，但其指标检测报告单的指标设置仍然比较混乱。报告单设计不合理的现象普遍存在。笔者为了纠正这种现象而撰写此文。研究指出了哪些是科学合理必须的指标和设置这些指标的两方面依据。论文阐明了全血高剪变率、中剪变率、低剪变率黏度，红细胞变形性、聚集性指标的正确含义，并将若干指标的优劣性进行了分析、比较。笔者为血液流变学首次提出了红细胞变形率、红细胞聚集率这两个新概念。研究揭示报告单指标设置不合理性归纳为三个方面：指标太多，指标重复，指标无意义。产生这些不合理性的缘由是：检测仪器厂商炫耀其仪器功能齐全，利于销售；设计者和检验人员血液流变学知识浅薄，指标良莠不分。但愿此文能引起人们重视，共同促进临床血液流变学指标设置和检测规范化。     

Nucleus classification in histology images using message passing network

Identification of nuclear components in the histology landscape is an important step towards developing computational pathology tools for the profiling of tumor micro-environment. Most existing methods for the identification of such components are limited in scope due to heterogeneous nature of the nuclei. Graph-based methods offer a natural way to formulate the nucleus classification problem to incorporate both appearance and geometric locations of the nuclei. The main challenge is to define models that can handle such an unstructured domain. Current approaches focus on learning better features and then employ well-known classifiers for identifying distinct nuclear phenotypes. In contrast, we propose a message passing network that is a fully learnable framework build on classical network flow formulation. Based on physical interaction of the nuclei, a nearest neighbor graph is constructed such that the nodes represent the nuclei centroids. For each edge and node, appearance and geometric features are computed which are then used for the construction of messages utilized for diffusing contextual information to the neighboring nodes. Such an algorithm can infer global information over an entire network and predict biologically meaningful nuclear communities. We show that learning such communities improves the performance of nucleus classification task in histology images. The proposed algorithm can be used as a component in existing state-of-the-art methods resulting in improved nucleus classification performance across four different publicly available datasets.     

Joint hub identification for brain networks by multivariate graph inference

Recent developments in neuroimaging allow us to investigate the structural and functional connectivity between brain regions in vivo. Mounting evidence suggests that hub nodes play a central role in brain communication and neural integration. Such high centrality, however, makes hub nodes particularly susceptible to pathological network alterations and the identification of hub nodes from brain networks has attracted much attention in neuroimaging. Current popular hub identification methods often work in a univariate manner, i.e., selecting the hub nodes one after another based on either heuristic of the connectivity profile at each node or predefined settings of network modules. Since the topological information of the entire network (such as network modules) is not fully utilized, current methods have limited power to identify hubs that link multiple modules (connector hubs) and are biased toward identifying hubs having many connections within the same module (provincial hubs). To address this challenge, we propose a novel multivariate hub identification method. Our method identifies connector hubs as those that partition the network into disconnected components when they are removed from the network. Furthermore, we extend our hub identification method to find the population-based hub nodes from a group of network data. We have compared our hub identification method with existing methods on both simulated and human brain network data. Our proposed method achieves more accurate and replicable discovery of hub nodes and exhibits enhanced statistical power in identifying network alterations related to neurological disorders such as Alzheimer's disease and obsessive-compulsive disorder.