Latest Issue
Issue 8 ， 2021
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Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses
Abstract：Toll-like receptor 3 (TLR3) is a member of the TLR family, mediating the transcriptional induction of type I interferons (IFNs), proinflammatory cytokines, and chemokines, thereby collectively establishing an antiviral host response. Studies have shown that unlike other TLR family members, TLR3 is the only RNA sensor that is utterly dependent on the Toll-interleukin-1 receptor (TIR)-domain-containing adaptor-inducing IFN-β (TRIF). However, the details of how the TLR3-TRIF signaling pathway works in an antiviral response and how it is regulated are unclear. In this review, we focus on recent advances in understanding the antiviral mechanism of the TRIF pathway and describe the essential characteristics of TLR3 and its antiviral effects. Advancing our understanding of TLR3 may contribute to disease diagnosis and could foster the development of novel treatments for viral diseases.Keywords：Toll-like receptor 3 (TLR3);Toll-interleukin-1 receptor (TIR)-domain-containing adaptor-inducing interferon-β (TRIF);Innate immune;Antiviral response- 170
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Published：2022-01-04 -
LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies
Abstract：Endometrial stromal tumors (ESTs) include endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Since these are rare tumor types, there is an unmet clinical need for the systematic therapy of advanced LG-ESS or HG-ESS. Cytogenetic and molecular advances in ESTs have shown that multiple recurrent gene fusions are present in a large proportion of LG-ESSs, and HG-ESSs are identified by the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE)-family with sequence similarity 22 (FAM22) fusion. Recently, a group of ESSs harboring both zinc finger CCCH domain-containing protein 7B (ZC3H7B)-B-cell lymphoma 6 corepressor(BCOR) fusion and internal tandem duplication (ITD) of the BCOR gene have been provisionally classified as HG-ESSs. In this review, we firstly describe current knowledge about the molecular characteristics of recurrent aberrant proteins and their roles in the tumorigenesis of LG-ESSs and HG-ESSs. Next, we summarize the possibly shared signal pathways in the tumorigenesis of LG-ESSs and HG-ESSs, and list potentially actionable targets. Finally, based on the above discussion, we propose a few promising therapeutic strategies for LG-ESSs and HG-ESSs with recurrent gene alterations.Keywords：Low-grade endometrial stromal sarcoma (LG-ESS);High-grade endometrial stromal sarcoma (HG-ESS);Molecular genetics;Therapeutics- 16
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Published：2022-01-04
Review
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Layers of interstitial fluid flow along a “slit-shaped” vascular adventitia
Abstract：Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6‒15.6 mm/s. These data revealed that a PACT pathway was a “slit-shaped” porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical “gel pump” is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.Keywords：Vascular adventitia;Interstitial fluid;Connective tissue;Interfacial zone- 14
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Published：2022-01-04 -
Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer
Abstract：Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489,and TMEM147-AS1,and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.Keywords：Bladder cancer;Copy number variation (CNV);Long non-coding RNA (lncRNA);Prognosis- 115
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Published：2022-01-04 -
Hemin-induced increase in saponin content contributes to the alleviation of osmotic and cold stress damage to
Conyza blinii in a heme oxygenase 1-dependent mannerAbstract：Hemin can improve the stress resistance of plants through the heme oxygenase system. Additionally, substances contained in plants, such as secondary metabolites, can improve stress resistance. However, few studies have explored the effects of hemin on secondary metabolite content. Therefore, the effects of hemin on saponin synthesis and the mechanism of plant injury relief by hemin in Conyza blinii were investigated in this study. Hemin treatment promoted plant growth and increased the antioxidant enzyme activity and saponin content of C. blinii under osmotic stress and cold stress. Further study showed that hemin could provide sufficient precursors for saponin synthesis by improving the photosynthetic capacity of C. blinii and increasing the gene expression of key enzymes in the saponin synthesis pathway, thus increasing the saponin content. Moreover, the promotion effect of hemin on saponin synthesis is dependent on heme oxygenase-1 and can be reversed by the inhibitor Zn-protoporphyrin-IX (ZnPPIX). This study revealed that hemin can increase the saponin content of C. blinii and alleviate the damage caused by abiotic stress, and it also broadened the understanding of the relationship between hemin and secondary metabolites in plant abiotic stress relief.Keywords：Hemin;Saponin;Conyza blinii;Heme oxygenase;Abiotic stress- 127
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Published：2022-01-04
Research Article
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Successful treatment of refractory pure red cell aplasia with eltrombopag after ABO-incompatible allogeneic hematopoietic stem cell transplantation
Keywords：纯红细胞再生障碍性贫血;异基因造血干细胞移植;艾曲波帕- 19
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Published：2022-01-04
Correspondence
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