Time filter

Source Type

Lung ischemia-reperfusion (I/R) injury remains one of the most common complications after various cardiopulmonary surgeries. The inflammation response triggered by the released damage-associated molecular patterns (DAMPs) aggravates lung tissue damage. However, little is known about the role of autophagy in the pathogenesis of lung I/R injury. Here, we report that a variety of inflammation-related and autophagy-associated genes are rapidly upregulated, which facilitate the inflammation response in a minipig lung I/R injury model. Left lung I/R injury triggered inflammatory cytokine production and activated the autophagy flux as evidenced in crude lung tissues and alveolar macrophages. This was associated with the release of DAMPs, such as high mobility group protein B1 (HMGB1) and heat shock protein 60 (HSP60). Indeed, treatment with recombinant HMGB1 or HSP60 induced autophagy in alveolar macrophages, whereas autophagy inhibition by knockdown of ATG7 or BECN1 markedly reduced DAMP-triggered production of inflammatory cytokines including IL-1β, TNF and IL12 in alveolar macrophages. This appeared to be because of decreased activation of MAPK and NF-κB signaling. Furthermore, knockdown of ATG7 or BECN1 inhibited Lys63 (K63)-linked ubiquitination of TNF receptor-associated factor 6 (TRAF6) in DAMP-treated alveolar macrophages. Consistently, treatment with 3-MA inhibited K63-linked ubiquitination of TRAF6 in I/R-injured lung tissues in vivo. Collectively, these results indicate that autophagy triggered by DAMPs during lung I/R injury amplifies the inflammatory response through enhancing K63-linked ubiquitination of TRAF6 and activation of the downstream MAPK and NF-κB signaling.Cell Death and Differentiation advance online publication, 3 February 2017; doi:10.1038/cdd.2017.1. © 2017 The Author(s)


Bao Y.,Second Military Medical University | Bao Y.,Shanghai University | Cao X.,Second Military Medical University
Journal of Autoimmunity | Year: 2015

B lymphocytes are generally recognized for their potential to mediate humoral immunity by producing different antibody isotypes and being involved in opsonization and complement fixation. Nevertheless, the non-classical, antibody-independent immune potential of B cell subsets has attracted much attention especially in the past decade. These B cells can release a broad variety of cytokines (such as IL-2, IL-4, IL-6, IL-10, IL-17, IFN-α, IFN-γ, TNF-α, TGF-β, LT), and can be classified into distinct subsets depending on the particular cytokine profile, thus emerging the concept of cytokine-producing B cell subsets. Although there is still controversy surrounding the key cell surface markers, intracellular factors and cellular origins of cytokine-producing B cell subsets, accumulating evidence indicates that these B cells are endowed with great potential to regulate both innate and adaptive arms of immune system though releasing cytokines. On the one hand, they promote immune responses through mounting Th1/Th2/Th17 and neutrophil response, inducing DC maturation and formation of lymphoid structures, increasing NK cell and macrophage activation, enhancing development of themselves and sustaining antibody production. On the other hand, they can negatively regulate immune responses by suppressing Th cell responses, inhibiting Tr1 cell and Foxp3+ Treg differentiation, impairing APC function and pro-inflammatory cytokine release by monocytes, and inducing CD8+ T cell anergy and CD4+ T cell apoptosis. Therefore, cytokine-producing B cell subsets have multifunctional functions in health and diseases, playing pathologic as well as protective roles in autoimmunity, infection, allergy, and even malignancy. In this review, we revisit the history of discovering cytokine-producing B cells, describe the identification of cytokine-producing B cell subsets, introduce the origins of cytokine-producing B cell subsets as well as molecular and cellular mechanisms for their differentiation, and summarize the recent progress made toward understanding the unexpectedly complex and potentially opposing roles of cytokine-producing B cells in immunological disorders. © 2014 Elsevier Ltd.


Cao X.,Chinese Institute of Basic Medical Sciences | Cao X.,Second Military Medical University
Nature Reviews Immunology | Year: 2016

In the initiation of innate immune responses against pathogens, pattern-recognition receptors (PRRs) have an essential role in recognizing specific components of microorganisms and triggering responses that eliminate the invading microorganisms. However, inappropriate activation of PRRs can lead to prolonged inflammation and even to autoimmune and inflammatory diseases. Thus, PRR-triggered responses are regulated through the degradation or translocation of the innate receptors themselves and through the involvement of intracellular regulators or amplifiers. In addition, a complex interplay between PRRs and/or other immune pathways finely tunes the outcome of host immune defence responses. In this Review, I describe many of the numerous distinct mechanisms for the self-regulation and cross-regulation of innate immune receptor signalling. © 2015 Macmillan Publishers Limited.


Yuan Y.-M.,Second Military Medical University | He C.,Second Military Medical University
Neuroscience Bulletin | Year: 2013

Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCI) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCI. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCI. © 2013 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg.


Qian C.,Second Military Medical University | Cao X.,Second Military Medical University | Cao X.,CAS Beijing National Laboratory for Molecular
Annals of the New York Academy of Sciences | Year: 2013

Toll-like receptors (TLRs) are critical pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs), which are conserved and specific molecular "signatures" expressed by pathogens. TLR ligation triggers distinct but shared signaling pathways that lead to effector mechanisms in innate immune responses. TLR specificity and activation are strictly and finely tuned at multiple levels of various signal transduction pathways, resulting in complex signaling platforms. Many molecules, ranging from membrane and cytosol to nuclear, contribute to TLR ligand discrimination or receptor signaling and play different roles in the regulation of TLR responses via different mechanisms, such as cross-regulation, protein modification, helper cofactors, and posttranscriptional and epigenetic regulation. Herein, we summarize the most recent literature that provides new insight into regulation of TLR signaling-triggered innate immune responses. A greater understanding of the mechanisms underlying the control of TLR signaling may provide new targets for therapeutic intervention for infections and inflammatory diseases. © 2012 The New York Academy of Sciences.


Xu S.,Second Military Medical University | Cao X.,Second Military Medical University
Cellular and Molecular Immunology | Year: 2010

Interleukin-17 (IL-17) and IL-17-producing cells have been shown to play important roles in inflammation and the immune response. IL-17 is believed to be mainly produced by T helper 17 (Th17) cells, a unique helper T-cell subset different from Th1 and Th2 cells. Other subsets of T cells such as γT and natural killer T (NKT) cells have also been found to produce IL-17 in response to innate stimuli. IL-17 acts as a proinflammatory cytokine that can induce the release of certain chemokines, cytokines, matrix metalloproteinases (MMPs) and antimicrobial peptides from mesenchymal and myeloid cells. This leads to the expansion and accumulation of neutrophils in the innate immune system and links innate and adaptive immunity in vivo. Furthermore, increasing evidence indicates that IL-17 and IL-17-producing cells are involved in the pathogenesis of various diseases such as allergies, autoimmune diseases, allograft transplantation and even malignancy. They may also play protective roles in host defense against infectious diseases and promote induction of cytotoxic T lymphocyte (CTL) responses against cancer. Targeting of the IL-17 axis is under investigation for the treatment of inflammatory disorders. © 2010 CSI and USTC. All rights reserved.


Liu Q.,Second Military Medical University
International Immunopharmacology | Year: 2011

Triptolide, a diterpene triepoxide, is a major active component of extracts derived from the medicinal plant Tripterygium wilfordii Hook F (TWHF). Triptolide has multiple pharmacological activities including anti-inflammatory, immune modulation, antiproliferative and ctyproapoptotic activity. So, triptolide has been widely used to treat inflammatory diseases, autoimmune diseases, organ transplantation and even tumors. Triptolide cannot only induce tumor cell apoptosis directly, but can also enhance apoptosis induced by cytotoxic agents such as TNF-α, TRAIL and chemotherapeutic agents regardless of p53 phenotype by inhibiting NFκB activation. Recently, the cellular targets of triptolide, such as MKP-1, HSP, 5-Lox, RNA polymerase and histone methyl-transferases had been demonstrated. However, the clinical use of triptolide is often limited by its severe toxicity and water-insolubility. New water-soluble triptolide derivatives have been designed and synthesized, such as PG490-88 or F60008, which have been shown to be safe and potent antitumor agent. Importantly, PG490-88 has been approved entry into Phase I clinical trial for treatment of prostate cancer in USA. This review will focus on these breakthrough findings of triptolide and its implications. © 2011 Elsevier B.V.


Patent
Second Military Medical University | Date: 2011-05-17

An indenoquinolone compounds of Formula (A) is disclosed, wherein the definition of each group is described in the description. These compounds may specifically inhibit topoisomerase I, and they have good activities against many kinds of human tumor cells, such as lung cancer, colon cancer, breast cancer, liver cancer and the like. They can be used in the manufacture of antitumor drugs. The method for preparing the compound of formula (A), and pharmaceutical compositions containing such compounds and the use in the manufacture of antitumor drugs are also disclosed.


Provided is a renal sarcomatoid cell line RCC09HYF, of which the deposit No. is CCTCC C201130, and the preparation method of the renal sarcomatoid cell line. The renal sarcomatoid cell line RCC09HYF can grow for a long period and be steadily passaged in vitro. By tumorigenic experiments using in-situ animal models in vitro it has been found that: the tumorigenesis is relatively fast inside animals and 3-4 weeks after tumor inoculation, the transplanted tumors fill the whole abdominal cavity, and dyscrasia appears in above 50% of nude mice; moreover, lung metastasis is present in a few individuals. The renal sarcomatoid cell line RCC09HYF can provide an effective and steady cell model for further study of the genesis and metastasis mechanism of renal sarcomatoid carcinoma in persons of Han nationality and for clinical prediction, diagnosis and treatment.


The present invention relates to the field of medical technology, and in particular, to a variety of substituted N-(5-(quinolin-6-yl)pyridin-3-yl) benzsulfamide derivatives represented by formula (1) (groups therein are as defined in the specification). The compounds according to the present invention have favorable anti-tumor activity against human lung cancer, colon cancer, liver cancer, breast cancer and glioblastoma multiforme, which contribute to development of highly effective, low toxic and high specific anti-tumor drugs, and have high value of development. The present invention also relates to a composition, preparation method and use thereof in the preparation of anti-tumor drugs.

Loading Second Military Medical University collaborators
Loading Second Military Medical University collaborators