Extracellular vesicles in bone and tooth: A state-of-art paradigm in skeletal regeneration

Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment.     

胰腺癌早期检测的生物标志物（英文）

胰腺癌症是最难诊断和治疗的恶性肿瘤之一,其特点是发病隐匿、进展迅速、预后差。目前,手术治疗仍然是首选治疗方法。然而由于缺乏早期症状,大约70%的患者在确诊时已经出现局部扩散或远端转移,从而无法进行手术治疗。由此看来,早期检测是提高患者治疗效果和预后的有效途径。临床上使用的成像方法 （CT、MRI、EUS等）通常无法检测早期病变,并且很容易受到操作员的影响。常规临床标志物如CA19-9、CA125、CA242和CEA受到限制,其敏感性或特异性不令人满意。因此,寻找新的具有高敏感性和特异性的标志物是实现胰腺癌早期检测的关键。近年来,对生物标志物的广泛研究主要集中在遗传学、转录组学和蛋白质组学上。特别是由microRNA(miRNA)、long non-coding RNA(lncRNA)和circRNA(circRNA)组成的非蛋白质编码RNA(non-protein coding RNA,ncRNA)为胰腺癌的早期检测提出了许多新思路。然而,其中绝大多数仍处于实验室研究阶段。而一项成熟的生物标志物研究应该整合基因组学、转录组学、蛋白质组学或代谢组学的数据,并结合患者的个体特征（如体重指数...     

Circulating adiposity-related microRNAs as predictors of the response to a low-fat diet in subjects with obesity

Recent studies have revealed the critical role of several microRNAs (miRNAs) in energy homeostasis and metabolic processes and suggest that circulating miRNAs can be used as early predictors of weight loss in the design of precision nutrition. Thus, the aim of this study was to investigate circulating adiposity-related miRNAs as biomarkers of the response to two specific weight loss dietary treatments. The expression of 86 miRNAs was investigated in plasma of 78 subjects with obesity randomized to two different diets [moderately high-protein diet (n = 38) and low-fat diet (n = 40)] and in 25 eutrophic controls (BMI ≤ 25 kg/m²). Bioinformatic analyses were performed to explore the target genes and biological pathways regulated by the dysregulated miRNAs. As results, 26 miRNAs were found differently expressed in eutrophic and volunteers with obesity. Moreover, 7 miRNAs (miR-130a-3p, miR-142-5p, miR-144-5p, miR-15a-5p, miR-22-3p, miR-221-3p and miR-29c-3p) were differentially expressed between responders and non-responders to a low-fat diet. Furthermore, after adjustment for basal glucose levels, 1-SD increase in miR-22-3p expression was associated with reduction in the risk of non-response to low-fat diet [OR = 0.181, 95% CI (0.084-0.947), P = .043]. Bioinformatic analyses evidenced that these 7 miRNAs regulate the expression of genes participating in important metabolic pathways. Conclusively, 7 circulating miRNAs related to adiposity could be used for predicting the response to a low-fat diet intervention prescribed to lose weight.     

Circulating exosomes repair endothelial cell damage by delivering miR-193a-5p

Circulating exosomes delivering microRNAs are involved in the occurrence and development of cardiovascular diseases. How are the circulating exosomes involved in the repair of endothelial injury in acute myocardial infarction (AMI) convalescence (3-7 days) was still not clear. In this study, circulating exosomes from AMI patients (AMI-Exo) and healthy controls (Normal-Exo) were extracted. In vitro and in vivo, our study showed that circulating exosomes protected endothelial cells (HUVECs) from oxidative stress damage; meanwhile, Normal-Exo showed better protective effects. Through the application of related inhibitors, we found that circulating exosomes shuttled between HUVECs via dynamin. Microarry analysis and qRT-PCR of circulating exosomes showed higher expression of miR-193a-5p in Normal-Exo. Our study showed that miR-193a-5p was the key factor on protecting endothelial cells in vitro and in vivo. Bioinformatics analyses found that activin A receptor type I (ACVR1) was the potential downstream target of miR-193a-5p, which was confirmed by ACVR1 expression and dual-luciferase report. Inhibitor of ACVR1 showed similar protective effects as miR-193a-5p. While overexpression of ACVR1 could attenuate protective effects of miR-193a-5p. To sum up, these findings suggest that circulating exosomes could shuttle between cells through dynamin and deliver miR-193a-5p to protect endothelial cells from oxidative stress damage via ACVR1.     

Role of miR-107 and its signaling pathways in diseases

Abstract

MicroRNAs exert their biologic effects by targeting specific mRNAs for degradation or translational inhibition. MicroRNA-mediated regulation is complex, potentially affecting expression of the host gene, related enzymes within the same pathway or apparently distinct targets. miR-107 is found to be implicated in the pathogenesis of some diseases. This review was performed to sum up the role of miR-107 and its signaling pathways in renal diseases.     

Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model

Abstract

Context: Accidental exposure to life-threatening radiation in a nuclear event is a major concern; there is an enormous need for identifying biomarkers for radiation biodosimetry to triage populations and treat critically exposed individuals.

Objective: To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice.

Methods: Mice were whole body irradiated with X-rays (2?Gy–15?Gy); blood was collected at various time-points post-exposure; total RNA was isolated; miRNA microarrays were performed; miRNAs differentially expressed in irradiated vs. unirradiated controls were identified; feature extraction and classification models were applied to predict dose-differentiating miRNA signature.

Results: We observed a time and dose responsive alteration in the expression levels of miRNAs. Maximum number of miRNAs were altered at 24-h and 48-h time-points post-irradiation. A 23-miRNA signature was identified using feature selection algorithms and classifier models. An inverse correlation in the expression level changes of miR-17 members, and their targets were observed in whole body irradiated mice and non-human primates.

Conclusion: Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.     

Clinical significance of the interaction between non-coding RNAs and the epigenetics machinery

Non-coding RNAs and epigenetics are remarkable mechanisms of cellular control. In this review we underline the processes by which non-coding RNAs (ncRNAs), shown to be involved in various diseases, are capable of modifying and being modified by the epigenetic machinery, emphasizing the clinical importance of this network in cancer. Many ncRNAs have been described that play important roles in the establishment and maintenance of the epigenome. However, only a few studies deeply take into account the role of ncRNAs from a clinicopathological standpoint. The wide range of interactions between the non-coding RNome and the epigenome, and the roles of these networks in the pathogenesis, prognosis and early diagnosis of many diseases, present new challenges and opportunities for future studies regarding therapeutic strategies in oncology.