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"Xiang, Li-xin"
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RIG-I： a multifunctional protein beyond a pattern recognition receptor
It was widely known that retinoic acid inducible gene I （RIG-I） functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent stud- ies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations. While in hepatocellular carcinoma and acute myeloid leukemia, RIG-I acts as a tumor suppressor through either augmenting STAT1 activation by competitively binding STAT1 against its negative regulator SliP1 or inhibiting AKT-mTOR signaling pathway by directly interacting with Src respectively. These new findings suggest that RIG-I plays more diverse roles in various cellular life activities, such as cell proliferation and differentiation, than previously known. Taken together, the function of RIG-I exceeds far beyond that of a pattern recognition receptor.
Journal Article
Occurrences and Functions of Ly6Chi and Ly6Clo Macrophages in Health and Disease
Macrophages originating from the yolk sac or bone marrow play essential roles in tissue homeostasis and disease. Bone marrow-derived monocytes differentiate into Ly6C hi and Ly6C lo macrophages according to the differential expression of the surface marker protein Ly6C. Ly6C hi and Ly6C lo cells possess diverse functions and transcriptional profiles and can accelerate the disease process or support tissue repair and reconstruction. In this review, we discuss the basic biology of Ly6C hi and Ly6C lo macrophages, including their origin, differentiation, and phenotypic switching, and the diverse functions of Ly6C hi and Ly6C lo macrophages in homeostasis and disease, including in injury, chronic inflammation, wound repair, autoimmune disease, and cancer. Furthermore, we clarify the differences between Ly6C hi and Ly6C lo macrophages and their connections with traditional M1 and M2 macrophages. We also summarize the limitations and perspectives for Ly6C hi and Ly6C lo macrophages. Overall, continued efforts to understand these cells may provide therapeutic approaches for disease treatment.
Journal Article
الثقة في النظرية : نجاح لنظام التنمية (البديل) الخاص بالصين
جاء هذا الكتاب تحت عنوان «الثقة في النظرية : نجاح لنظام التنمية \"البديل\" الخاص بالصين» وهو من تأليف (مايا غيو) وترجمة عبد الرحمن النجار. يبحث الكتاب في التطور الصيني السريع خلال الستة عقود الماضية، والدور الذي لعبه الحزب الشيوعي الصيني في تحويل الصين إلى دولة اشتراكية حديثة مزدهرة وقوية وديمقراطية ومتطورة ثقافيا ويستكشف ويستكشف فيما إذا كان صعود الصين يهدد نموذج التنمية الغربي وخاصة بعد أن أضحى صعود الصين حقيقة لا جدال فيها. يعتبر هذا الكتاب من أنجح الكتب التي نشرت عن الصين اليوم. فهو يقدم حججا مقنعة حول نهوض الصين. وتستند الآراء المعبر عنها في الكتاب ليس فقط إلى 60 عاما من تاريخ جمهورية الصين الشعبية وإنجازاتها الملحوظة في العقود الثلاثة الماضية، ولكن أيضا على تاريخها الحديث منذ عام 1840، وتاريخها الذي دام 2000 عام كدولة موحدة، وحضارتها ذات ال 5000 سنة. وتعكس المقابلات التي أجرتها المؤلفة \"مايا غيو\" مراقبتها الدقيقة للصين اليوم. إذ تضمنت أشخاصا من دوائر مختلفة، تشمل مجالات خبرتهم السياسة والاقتصاد والمجتمع والوضع الوطني وتاريخ دبلوماسية الحزب الشيوعي الصيني والاستراتيجية العسكرية وإدارة ممتلكات الدولة والرعاية الصحية والأعمال التجارية الخاصة. وتختلف موضوعات المقابلات على نطاق واسع؛ فمن النظم والنظرية والتطوير والإصلاح، إلى نوعية الحياة والاستراتيجية والدبلوماسية وجميع من كان فيها يؤيدون التعلم من الحضارات الإنسانية، ولكنهم يصرون في الوقت نفسه على ضرورة اتخاذ مسار يناسب الصين بدلا من استنساخ النموذج الغربي. يأتي هذا الكتاب من ضمن سلسلة تتألف من ثلاثة كتب وهي : الثقة في المسار : نموذج جديد لقوة صاعدة، الثقة في النظرية : فلسفة الصين لنظام دولي جديد، والثقة في النظام : نجاح نظام التنمية \"البديل\" في الصين. بما يوفر للقارئ مقاربة نظرية وواقعية لمسار الصين ونظريتها ونظامها، ويشرح أسباب ثقة الدولة الصينية في خياراتها.
Book
Single-cell RNA sequencing unveils the hidden powers of zebrafish kidney for generating both hematopoiesis and adaptive antiviral immunity
The vertebrate kidneys play two evolutionary conserved roles in waste excretion and osmoregulation. Besides, the kidney of fish is considered as a functional ortholog of mammalian bone marrow that serves as a hematopoietic hub for generating blood cell lineages and immunological responses. However, knowledge about the properties of kidney hematopoietic cells, and the functionality of the kidney in fish immune systems remains to be elucidated. To this end, our present study generated a comprehensive atlas with 59 hematopoietic stem/progenitor cell (HSPC) and immune-cells types from zebrafish kidneys via single-cell transcriptome profiling analysis. These populations included almost all known cells associated with innate and adaptive immunity, and displayed differential responses to viral infection, indicating their diverse functional roles in antiviral immunity. Remarkably, HSPCs were found to have extensive reactivities to viral infection, and the trained immunity can be effectively induced in certain HSPCs. In addition, the antigen-stimulated adaptive immunity can be fully generated in the kidney, suggesting the kidney acts as a secondary lymphoid organ. These results indicated that the fish kidney is a dual-functional entity with functionalities of both primary and secondary lymphoid organs. Our findings illustrated the unique features of fish immune systems, and highlighted the multifaced biology of kidneys in ancient vertebrates.
Journal Article
Genome Sequencing of the Perciform Fish Larimichthys crocea Provides Insights into Molecular and Genetic Mechanisms of Stress Adaptation
The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea.
Journal Article
Coordination of Bactericidal and Iron Regulatory Functions of Hepcidin in Innate Antimicrobial Immunity in a Zebrafish Model
Hepcidin acts as both an antimicrobial peptide and a hormonal regulator of iron homeostasis; however, the biological significance of this dual-function in immune reactions remains elusive. In this study, we provide experimental evidence regarding the coordination of this dual-function in the innate antimicrobial immunity using a zebrafish model. The transcription of hepcidin gene was significantly upregulated in liver by
Aeromonas hydrophila
(
A.h
) DNA stimulation, which was accompanied by an increase of hepcidin protein and a decrease of iron concentration in serum. Thus, an enhanced bactericidal activity against
A.h
and
Escherichia coli
and inhibitory effects on
A.h
growth and OmpA expression were observed in
A.h
cells, the latter of which made the bacterium more susceptible to complement attack. The enhanced bacteriostatic activities in serum following the stimulation were dramatically impaired by neutralizing hepcidin or restoring iron to the samples. Immuno-protection assay showed that zebrafish administrated with
A.h
DNA or designed CpG-ODNs had a significantly enhanced defence against
A.h
and
Vibrio alginolyticus
infections, which was also eliminated by the neutralization of hepcidin. Results indicate that the induction of hepcidin leads to the decrease of iron in circulation, which eventually limits iron availability to invading microorganisms, thus contributing to host defence.
Journal Article
The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway
Background/Aims: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. Methods: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells. The CCK-8 assay, wound healing assay, and Transwell assay were used to detect cell proliferation, migration and invasion, respectively. Western blotting and luciferase activity assays were used to identify CRNDE and TCF7L2 as one of the direct targets of miR-217. The activity of the Wnt/β-catenin signaling pathway was analyzed by the TOPflash assay, and the subcellular localization of β-catenin and TCF7L2 was analyzed by western blotting and confocal microscopy. Results: In this study, we found that high expression of CRNDE is negatively correlated with low expression of miR-217 in colorectal cancer tissue and colorectal cancer cells. The dual luciferase reporter analysis showed that miR-217 is bound to CRNDE and TCF7L2 and negatively regulate their expression. CRNDE down-regulation inhibited the cell proliferation, migration and invasion in vitro and in vivo and the inhibitions were both completely blocked after miR-217 inhibition or TCF7L2 overexpression. Finally, TOPflash analysis showed that the activity of Wnt/β-catenin signaling is inhibited by CRNDE down-regulation and rescued by TCF7L2 over-expression. Consistently immunostaining and western blotting analysis showed that the expression of b-catenin and TCF7L2 in the nucleus was significantly decreased by CRNDE down-regulation and was rescued by TCF7L2 over-expression. Conclusions: The present study suggest that CRNDE involves in the cell proliferation, migration and invasion of colorectal cancer cells via increasing the expression of TCF7L2 and activity of Wnt/β-catenin signaling through binding miR-217 competitively.
Journal Article
Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity
γδ T cells represent an evolutionarily primitive T cell subset characterized by distinct T cell receptors (TCRs) and innate and adaptive immune functions. However, the presence of this T cell subset in ancient vertebrates remains unclear. In this study, γδ T cells from a zebrafish (
) model were subjected to molecular and cellular characterizations. The constant regions of zebrafish TCR-γ (
TRGC) and δ (
TRDC) were initially identified. Zebrafish γδ T cells accounted for 7.7-20.5% of the total lymphocytes in spleen, head kidney, peripheral blood, skin, gill, and intestine tissues. They possess typical morphological features of lymphocytes with a surface phenotype of γ
δ
CD4
CD8
. Zebrafish γδ T cells functionally showed a potent phagocytic ability to both soluble and particulate antigens. They can also act as an antigen-presenting cell to initiate antigen (KLH)-specific CD4
T
cell activation and to induce B cell proliferation and IgM production. Particularly, zebrafish γδ T cells also play a critical role in antigen-specific IgZ production in intestinal mucus. These findings demonstrated that γδ T cells had been originated as early as teleost fish, which providing valuable insights into the evolutionary history of T cell subset. It is anticipated that this study would be used as a guide to develop a zebrafish model for the cross-species investigation of γδ T cell biology.
Journal Article