Emotional regulation of pain: the role of noradrenaline in the amygdala

The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.     

Effective suppression of fibronectin synthesis by retrovirus delivered shRNA in rat cardiac fibroblasts

Ventricular remodeling plays a central role in chronic heart failure. Fibrosis is an important manifest of ventricular remodeling. Fibrosis is a disproportion-ate accumulation of extracellular matrix (ECM). Fi-brosis stiffens the ventricles and impedes both con-traction and relaxation. Furthermore, fibrosis results in reduced capillary density and an increased oxygen diffusion distance that can lead to hypoxia of myo-cytes. Thus, inhibiting the fibrosis profoundly affects myocyte metabolism …     

Differential modulation by AMPA of signals from red- and green-sensitive cones in carp retinal luminosity-type horizontal cells

Intracellular recordings were made from luminosity-type horizontal cells (LHCs) in the isolated superfused carp retina and the effect of AMPA (α-amino-3-hydroxy-5-methylisoxa-zole-4-propionic acid), a glutamate receptor agonist, on these cells was studied. AMPA suppressed the responses of LHCs driven by red-sensitive (R-) cones whereas it potentiated the responses driven by green-sensitive (G-) cones. The AMPA effect could be completely blocked by GYKI 53655, a specific AMPA receptor antagonist, indicating the exclusive involvement of AMPA-preferring receptors. The AMPA effect persisted in the presence of picrotoxin (PTX) or di-hydrokainic acid (DHK), suggesting that the feedback from LHCs onto cones and glutamate transporters on cones may not be involved. It is suggested that there may exist different AMPA receptor subtypes with distinct characteristics on LHCs, which mediate signal transfer from R- and G-cones to LHCs, respectively.     

Expression of tPA, LH receptor and inhibin α, β_A subunits during follicular atresia in rats

By using DNA 3'-end labeling, immunocytochemistry and mRNA in situ hybridization detection techniques, the expression of inhibin subunits and LH receptor in the granulosa cells and tissue-type plasminogen activator (tPA) in the oocytes has been studied in relation to follicular development and atresia. The results demonstrated that: (ⅰ) tPA activity in the oocytes of normal developing follicles is undetectable, and increases significantly in the follicle undergoing atresia; (ⅱ) the production of inhibin subunits in granulosa cells is negatively correlated with the expression of oocyte tPA activity, indicating that they may be an important regulator of oocyte tPA production and follicular development; (ⅲ) in atretic follicles, granulosa cells do not express LH receptor and inhibin subunits. It is therefore suggested that tPA may play a role in oocyte self-destruction and clearance in some of atretic follicles, and inhibin of granulosa-origin might be an inhibitory factor for the translation of tPA in     

CaMKIIα and caveolin-1 cooperate to drive ATP-induced membrane delivery of the P2X3 receptor

The P2X3 receptor plays a vital role in sensory processing and transmission. The assembly and trafficking of the P2X3 receptor are important for its function in primary sensory neurons. As an important inflammation mediator, ATP is released from different cell types around primary sensory neurons, especially under pathological pain conditions. Here, we showthat α, β-MeATP dramatically promoted membrane delivery of the P2X3 receptor both in HEK293T celts expressing recombinant P2X3 receptor and in rat primary sensory neurons. α, β-MeATP induced P2X3 receptor-mediated Ca^2＋ influx, which further activated Ca^2＋/calmodulin-dependent protein kinase Ilec （CaMKIIα）. The N terminus of the P2X3 receptor was responsible for CaMKIleα binding, whereas Thr38s in the C terminus was phosphorylated by CaMKIIα. Thr^388 phosphorylation increased P2X3 receptor binding to caveoUn-1. CaveoUn-1 knockdown abrogated the α, β-MeATP-induced membrane insertion of the P2X3 receptor. Moreover,α, β-MeATP drove the CaMKIlec-mediated membrane coinsertion of the P2X2 receptor with the P2X3 receptor. The increased P2X3 receptors on the cell membrane that are due to Thr388 phosphorytation facilitated P2X3 receptor-mediated signal transduction. Together, our data indicate that CaMKIIoL and caveoUn-1 cooperate to drive Ugand-induced membrane delivery of the P2X3 receptor and may provide a mechanism of P2X3 receptor sensitization in pain development.     

The progress of abnormal expression of Lutheran blood group glycoprotein in cancers

Lutheran blood group glycoprotein (Lu-gp) is a specific α5 laminin receptor that is linked by binding to its receptor in the basement membrane matrix. Although the biological function of Lu-gp is unknown, its special affinity with laminin in the chain suggests that it plays an important role in human development and physiological processes. As the interaction between Lu-gp and laminin is further investigated, their expression may be found to play an important role in tumor invasion and metastasis. Laminin receptors help cells adhere, receive and conduct extracellular information into cells, mainly through MAPK pathways, including ERKs, p38MAPK, etc., affecting the degradation of the extracellular matrix and enhancing tumor cell infiltration and metastasis. Present researches in cancers mainly focus on aspects relating to laminin, but largely do not pay attention to the Lutheran blood group antigen, basal cell adhesion molecule. This paper focuses on the abnormal expression of the laminin receptor, that is, the Lutheran blood group antigen, in cancers, which is of great significance to the mechanism of cancer invasion and metastasis, and for finding effective treatment methods for cancers.     

Construction of Y376C-FGFR4 eukaryotic expression plasmid and its biological activity in HEK293 cell

Fibroblast growth factor receptor （FGFR）, a member of tyro- sine kinase family, is composed of three domains, including a three-extracellular Ig-like domain, a transmembrane domain, and a tyrosine kinase domain. FGFR4 is a member of the FGFR family, which plays a pivotal role in tumorigenesis. It has been found that FGFR4 plays an important role in melan- oma, prostate cancer, head and neck cancer, and primary liver cancer malignant development [1,2]. The poor response of FGFR4 to chemotherapy has been associated with its over-expression [3].     

Waldenström macroglobulinemia – immunophenotype and natural history

Despite encouraging progress in recent years, our knowledge of the natural history of Waldenstr?m macroglobulinemia (WM), a low-grade LPL (lymphoplasmacytic lymphoma) of mature IgM⁺ B-lymphocytes, remains superficial. This is particularly true of the etiology of WM (tumor causation and initiation) and the sequence of events that underlie the malignant transformation of precursor B cells (tumor progression). Here we briefly review the epidemiology of and genetic predisposition to WM and consider the role of autoimmunity and chronic inflammation in related tumor development. We discuss the immunophenotypic features of WM, including the immunological specificity of WM-associated IgM paraproteins. The proclivity of patients with WM to develop the rare immunoglobulin autoantibody syndromes mixed IgM-IgG cryoglobulinemia, chronic cold agglutinin disease, and IgM neuropathy will also be discussed. We conclude with a call for additional research to elucidate outstanding questions, such as the role of T cell-dependent vs. –independent immune responses in the pathophysiology of WM.     

Recent progress on mechanisms of human cognition and brain disorders

正Human cognition plays a crucial role in our daily life. It enables us to perceive a constant influx of inputs, to memorize the scenarios, and to reason or decide their outcomes (Thagard, 2005). Abnormal cognitive function, which is usually involved in neurological and mental diseases, such as chronic pain, mood disorders, autism, dementia, often seriously deteriorates individuals’ life quality and brings inexhaustible social problems.     

Nor1, a novel cytokine-responsive regulator of pancreatic β-cell mass and function mediated by disruption of mitochondrial networks

Type 2 diabetes(T2D)is a chronic metabolic disease characterized by insulin resistance and hyperglycemia,which is ultimately linked to the loss of pancreaticβ-cells and their function[1].Understanding the pathological mechanisms ofβ-cell dysfunction in T2D may lead to development of new therapeutic approaches.Recently,compelling evidence suggests that members of the nuclear receptor 4A(NR4A)subgroup play a pivotal role inβ-cell loss[2].Nor1,also known as NR4A3,belongs to the NR4A subfamily,which also includes Nur77(NR4A1)and Nurr1(NR4A2),and is defined as a true orphan nuclear receptor with an unknown endogenous ligand or ligand independent[3].As a regulator of gene expression located in the nucleus,Nor1 exhibits tissue-specific expression,which selectively controls diverse biological processes,including cell proliferation,apoptosis,differentiation,immune homeostasis,and fuel utilization[4].Thus far,it was reported that Nor1 is involved in numerous pathologies such as cancer,inflammatory diseases,and Parkinson’s disease[4].     

Melatonin: A master regulator of plant development and stress responses

Melatonin is a pleiotropic molecule with multiple functions in plants. Since the discovery of melatonin in plants, numerous studies have provided insight into the biosynthesis, catabolism, and physiological and biochemical functions of this important molecule. Here, we describe the biosynthesis of melatonin from tryptophan, as well as its various degradation pathways in plants. The identification of a putative melatonin receptor in plants has led to the hypothesis that melatonin is a hormone involved in regulating plant growth,aerial organ development, root morphology, and the floral transition. The universal antioxidant activity of melatonin and its role in preserving chlorophyll might explain its anti-senescence capacity in aging leaves. An impressive amount of research has focused on the role of melatonin in modulating postharvest fruit ripening by regulating the expression of ethylene-related genes.Recent evidence also indicated that melatonin functions in the plant's response to biotic stress,cooperating with other phytohormones and wellknown molecules such as reactive oxygen species and nitric oxide. Finally, great progress has been made towards understanding how melatonin alleviates the effects of various abiotic stresses, including salt, drought, extreme temperature, and heavy metal stress. Given its diverse roles, we propose that melatonin is a master regulator in plants.     

Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone

The thyroid hormones L-thyroxine and triiodo-Lthyronine have profound effects on postenbryonic development of most vertebrates.Analysis of their action in mammals is vitiated by the exposure of the developing foetus to a number of maternal factors which do not allow one to specifically define the role of thyroid hormone (TH) or that of other hormones and factors that modulate its action.Amphibian metamorphosis is obligatorily dependent on TH which can initiate all the diverse physiological manifestations of this postembryonic developmental process(morphogenesis,cell death,re-structuring,etc.) in free-living embryos and larvas of most anurans.This article will first describe the salient features of metamorphosis and its control by TH and other hormones.Emphasis will be laid on the key role played by TH receptor (TR),in particular the phenomenon of TR gene autoinduction,in initiating the developmental action of TH.Finally,it will be argued that the findings on the control of amphibian metamorphosis enhance our understanding of the regulation of postembryonic development by TH in other vertebrate species.     

Matrix metalloproteinases and their expression in mammary gland

The matrix metalloproteinases (MMPs) are a family of zine-dependent endopeptidases that play a key role in both normal and pathological processes involving tissue remodeling events.The expression of these proteolytic enzymes is highly regulated by a balance between extracellular matrix (ECM) deposition and its degradation,and is controlled by growth factors,cytokines,hormones,as well as interactions with the ECM macromolecules.Furthermore,the activity of the MMPs is regulated by their natural endogenous inhibitors,which are members of the tissue inhibitor of metalloproteinases (TIMP) family.In the normal mammary gland,MMPs are expressed during ductal development,lobulo-alveolar development in pregnancy and involution after lactation.Under pathological conditions,such as tumorigenesis,the dysregulated expression of MMPs play a role in tumor initiation,progression and malignant conversion as well as facilitating invasion and metastasis of malignant cells through degradation of the ECM and basement membranes.