Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.

Insulin exerts direct, IGF-1 independent actions in growth plate chondrocytes

Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor （IR） selectively in chondrocytes （CartIR-/-） had no discernable differences in total femoral length compared to control littermates. However, CartIR-/- mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor （IGF）-IR mRNA and protein levels. Subsequently, IGF-1 induced phosphorylafion of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR-/- mice when compared with that of the control littermates, which was associated with upregnlation of tuberous sclerosis complex 2 （TSC2）. These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.

精准医学发展趋势:从定量成像到放射组学（英文）

放射学(影像学)及影像引导的介入手段能提供多参数的形态学及功能信息,在精准医学中扮演着越来越重要的角色。因此,放射科医生需要理解影像表型,并将这些表型与潜在的疾病相关联,进而描述图像特征。但是为了能理解并描述异质性实体肿瘤的分子表型(基因组学信息),就需要通过活检取得这些组织更进一步的序列信息。因此,放射科医生为了能获得详尽的影像表型,需要从不同视图和角度采集图像,而这就产生了大量的数据。从所有这些影像数据中提取有意义的细节非常具有挑战性,并衍生出了大数据这个命题。因为影像组学有对诊断支持提供有意义的诠释性和预测性信息的潜力,所以近年来对于影像组学的关注越来越多。影像组学是传统的计算机辅助诊断、深度学习和人类技能的结合,因此它能被用来定量描述肿瘤表型。本文对影像组学流程的概览、基于不同手段(如计算机断层扫描(CT)、磁共振成像(MRI)和正电子发射计算机断层扫描(PET))的影像组学研究结果、面临的挑战和影像组学对于精准医学潜在的贡献等方面进行了讨论。

Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage

Background and purpose Signal transducer and activator of transcription 3(STAT3)may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses.Thus,this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage(SAH).Methods The SAH model was established by endovascular perforation in the mouse.Real-time PCR(RtPCR)and western blot were used to examine the dynamic STAT3 signalling pathway responses after SAH.To clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH,the microglia-specific STAT3 knockout(KO)mice were generated by the Cre-LoxP system.The neurological functions were assessed by Catwalk and Morris water maze tests.Neuronal loss after SAH was determined by immunohistochemistry staining.Microglial polarisation status after STAT3 KO was then examined by RtPCR and immunofluorescence.Results The STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after SAH.Downstream factors and related mediators altered dynamically and accordingly.Microglial STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after SAH.To investigate the underlying mechanism,we examined the microglial reaction after STAT3 KO.STAT3 deletion reversed the increase of microglia after SAH.Loss of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 polarisation.Functionally,microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early phase.Conclusions STAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent neuroinflammation.Microglial STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inflammatory responses after SAH.STAT3 may serve as a promising therapeutic target to alleviate early brain injury after SAH.