ABSTRACT
Fibrosis is a pathological process characterized by tissue scars and can occur in many organs of the human body. Organ fibrosis is manifested by increased fibrous connective tissue and reduced parenchymal cells in organ tissues, which can lead to destruction of organ structures and reduced function, which seriously endangers human health. Current strategies for treating organ fibrosis include: blocking the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, anti-inflammatory, regulating the sphingosine kinase 1/sphingosine-1-phosphate (SK1/S1P) signaling pathway, antagonizing vasoactive peptide receptors, enzyme inhibitors, kinase inhibitors, inhibitors of cellular signaling pathway, regulation of metabolic pathways, and mesenchymal stem cell therapy. In the review, the treatment strategies for organ fibrosis and the latest developments in the research of anti-organ fibrosis drugs are summarized to provide a reference for the development of anti-organ fibrosis drugs.
ABSTRACT
Investigating the influence of acupuncture on cellular signal transduction is an efficient pathway to reveal the action mechanism of acupuncture on spinal cord injury (SCI). In this study, the experiment research literature regarding acupuncture for SCI during past 10 years was reviewed and analyzed. As a result, it was found that acupuncture could regulate the expression of the first intercellular messenger as well as the second signal molecules including cyclic adenosine monophosphate, cyclic guanosine monophosphate, Ca2+, nitric oxide to intervene the apoptotic signaling pathway, Rho/Rock signaling pathway, Wnt signaling pathway, MAPK signaling pathway, Notch signaling pathway, etc., which could improve regeneration and repair of SCI. In conclusion, in future researches more attention should be paid to the cellular signal transduction networks and different effects among various acupoint combinations and acupuncture modalities on cellular signal transduction, which have an essential role for revelation of clinical application rules and optimization of clinical treatment protocol.
ABSTRACT
Inflammation reaction and immune response are inseparable at the levels of system, tissue, cell and molecule. Inflammatory immune responses (IIR) is defined a moderate or abnormal system responses of inflammatory immune related cells in responding to the internal and external environ-ment changes of body. Inflammatory immune related cells (traditionally, eg, macrophages, dendritic cells, T cells and B cells, etc, and non- traditionally, eg, glial cells, endothelial cells, epithelial cells, fibroblasts, synovial cells and liver cells, etc), and cytokines/receptor signal transduction involved in IIR. In current clinic drugs, such as inhibitors of COXs, inhibitors of TNF-alpha, IL-6, IL-17, BAFF etc, tradi?tional immunosuppressive drugs (eg, methotrexate, leflunomide) and novel kinase inhibitor (eg, JAKs inhibitor), suppress enzyme activity, gene synthesis and transcription, cytokines and receptor signal, etc, respectively. These drugs restrain the excessive activation function of inflammatory immune related cells, but at the same time, also inhibit the physiological response of these cells to signaling molecules, which cause physiological function disorder of cells and tissues, increase the risks of serious adverse drug reaction including infection and cancer. Soft regulation of inflammatory immune responses (SRIIR), that is regulating the activity of key molecules or interaction between molecules in cells and resulting in making excessive activation function back to normal physiological levels, is a novel direction of discovery and development of new drugs for the treatment of IIR related diseases.
ABSTRACT
Since last century, drug discovery efforts mostly focus on searching for chemicals which can inhibit some specific steps in a well-described disease pathway. However, this kind of highly specific inhibitors can not be effective for complex diseases, like cancer, diabetes, schizophrenia and mental illness. Therefore, we need to rethink the drug discovery and therapeutic strategies. In this review, the strategies of selection of cellular signal transduction networks and their dynamics as the targets for drug discovery and pharmacological treatments will be discussed. The properties and analytical methods of these signal transduction networks, internet sources and software tools for performing these strategies will be described. Strategies and procedures of using network- based drug discovery will be emphasized, including multi-targets drug design and network-based drug discovery.
ABSTRACT
Activator protein-1(AP-1) is a collective term referring to dimeric transcription factors composed of Jun protein family and Fos protein family that bind to the AP-1 sites of many genes,also known as TPA-responsive elements.AP-1 involves in the gene transcriptional regulation of a large number of growth factors and cytokines and leads to a series of physiological and pathophysiological changes of the body.Increasing attention has been paid to the relationship between AP-1 and the allergic diseases in recent years.This article reviewed the structure?activation of AP-1,and the relationship between AP-1 and the allergic diseases.
ABSTRACT
Cellular signal transduction plays an important role in pathogenesis of myocardial ischemia reperfusion(MIR) injury. During this process, extracellular signal molecules, membrance receptors and intracellular signal paths are involved. There are many cross talkings in signal pathways at many levels. The present article reviews cellular signal transduction mechanisms in MIR. The exploration of MIR's cellular pathogenesis may be beneficial for us to prevent and cure the heart damage in clinic. Furthermore, it may provide a new way of thinking in mechanism research of medicine.