Roles of atypical chemokine receptors in progression and metastasis of tumor

Chemokines and their receptors have been implicated mostly in tumor progression and metastasis. Atypical chemokine receptors (ACKRs) comprise a group of 7-transmembrane domain proteins structurally similar to G protein-coupled receptors. However, ACKRs do not induce classical signaling via the typical G protein-mediated pathways. ACKRs efficiently internalize the cognate chemokine ligands and act as scavengers instead. ACJRs are composed of at least 3 members of chemokine receptors:Duffy antigen receptor for chemokines (DARC, also known as ACKR1), D6 (also known as ACKR2) and ChemoCentryx chemokine receptor (CCX-CKR, also known as ACKR4). These receptors bind to and/or internalize their chemoattractant ligands without activating signal transduction cascades leading to cell migration. In this review, we summarize the recent progress regarding the roles of ACKRs in the progression and metastasis of tumor.     

挪威云杉幼树韧皮部挥发性物质的测定

通过GC-MS测定挪威云杉幼树主干上部与下部韧皮主要挥发性物质的化学成分与含量，结果表明挪威云杉幼树的韧皮部挥发性物质的主要成分为α-蒎烯、茨烯、β-蒎烯、月桂烯、3-蒈烯、柠檬烯、β-水芹烯7种单萜化合物。α-蒎烯、β-蒎烯、月桂烯、3-蒈烯、β-水芹烯的含量在上部韧皮与下部韧皮有明显差异，其中上部韧皮部α-蒎烯、β-蒎烯和β-水芹烯的含量明显高于下部主干韧皮部,这为解释松树皮象的取食习性，打下了基础。     

Probiotic Lactobacillus acidophilus bacteria or synthetic TLR2 agonist boost the growth of chicken embryo intestinal organoids in cultures comprising epithelial cells and myofibroblasts

The intestinal epithelial cells reside in close proximity to myofibroblasts and microbiota, which are supposed to have an impact on intestinal stem cells fate and to influence processes of tissue maturation and regeneration. Mechanism underlying these phenomena and their diversity among vertebrates can be studied in 3D organoid cultures. We investigated the growth of chicken embryo intestinal epithelial organoids in Matrigel with and without Toll-like receptors (TLRs) stimulation. The organoid cultures contained also some myofibroblasts with potential to promote intestinal stem cell survival. Organoid cells, expressing TLR4, TLR2 type 1 and TLR2 type 2 were incubated with their agonists (lipopolysaccharide – LPS and Pam3CSK4) or co-cultured with Lactobacillus acidophilus bacteria (LA-5). Pam3CSK4 and LA-5 promoted organoid growth, which was demonstrated by comparing the morphological parameters (mean number and area of organoids). The profile of prostaglandins (PG), known to promote intestinal regeneration, in supernatants from organoid and fibroblast cultures were evaluated. Both PGE₂ and PGD₂ were detected. As compared to unstimulated controls, supernatants from the Pam3CSK4-stimulated organoids contained twice as much of PGE₂ and PGD₂. The changes in production of prostaglandins and the support of epithelial cell growth by myofibroblasts are factors potentially responsible for stimulatory effect of TLR2 activation.     

Molecular Cloning,Sequence Analysis and Tissues Expression Profile of Part of Mink Toll-like Receptors (TLRs) Genes

The present study was aimed to explore the potential role of Toll-like receptors (TLRs) on the mink immunity, and accumulate alternative genetic material for the mink breeding for disease-resistant.Four pairs of primers were designed according to ferret TLR sequences in GenBank to obtain the sequences of TLR genes (TLR4, TLR6, TLR7 and TLR8) of mink and then performed bioinformatics analysis of these sequences.In addition, the expression of TLR4 and TLR7 genes in various tissues in young and adult minks were analyzed by RT-PCR. Sequence homology analysis showed that mink had higher homology with carnivora (ferrets, polar bear, panda, walrus, seals, dog, tiger and cat) which had the nearest perimeter in the phylogenetic tree.Tissue expression analysis showed that TLR4 and TLR7 were widely and differently expressed in variety tissues of mink.Interestingly, the expression of TLR4 and TLR7 in young mink were much higher than that in adult mink.     

Pharmacological and therapeutic targets for Δ9 tetrahydrocannabinol and cannabidiol

Summary Cannabis is the unique source of a set of at least 66 compounds known collectively as cannabinoids. Of these, most is known about the pharmacology of ⁹-tetrahydrocannabinol (⁹-THC), the main psychoactive constituent of cannabis, and about cannabidiol (CBD), which lacks psychoactivity. Accordingly, this paper focuses on the pharmacological and therapeutic targets of these two cannabinoids. Many of the effects of ⁹-THC are mediated by cannabinoid receptors of which at least two types, CB₁ and CB₂, are present in mammalian tissues. Endogenous agonists for cannabinoid receptors have also been discovered. CB₁ receptors are present at the terminals of central and peripheral neurones, where they modulate transmitter release. They also exist in some non-neuronal cells. CB₂ receptors are expressed mainly by immune cells, one of their roles being to alter cytokine release. ⁹-THC also appears to have non-CB₁, non-CB₂ pharmacological targets. It is already licensed for clinical use in the U.S.A. as an anti-emetic and appetite stimulant and both ⁹-THC and ⁹-THC-rich cannabis extracts show therapeutic potential as neuroprotective and anticancer agents and for the management of glaucoma, pain and various kinds of motor dysfunction associated, for example, with multiple sclerosis and spinal cord injury. CBD has much less affinity for CB₁ and CB₂ receptors than ⁹-THC and its pharmacological actions have been less well characterized. Potential clinical applications of CBD and CBD-rich cannabis extracts include the production of anti-inflammatory and neuroprotective effects, the management of epilepsy, anxiety disorders, glaucoma and nausea, and the modulation of some effects of ⁹-THC.     

Transition period-related changes in the abundance of the mRNAs of adiponectin and its receptors,of visfatin,and of fatty acid binding receptors in adipose tissue of high-yielding dairy cows

Adipose tissue expresses adipokines, which are involved in regulation of energy expenditure, lipid metabolism, and insulin sensitivity. To adapt for the transition from pregnancy to lactation, particularly in high-yielding dairy cows, adipokines, their receptors, and particular G-protein coupled receptors (GPRs) are of potential importance. Signaling by GPR 41 stimulates leptin release via activation by short-chain fatty acids; GPR 43/109A inhibits lipolysis, and GPR 109A thereby mediates the lipid-lowering effects of nicotinic acid and β–hydroxybutyrate. The aim of this study was to compare the mRNA expression of adiponectin and visfatin, adiponectin receptors 1 and 2 (AdipoR1/2), leptin receptor (obRb), insulin receptor as of the aforementioned GPRs during the transition period in high-yielding dairy cows. Biopsies from subcutaneous fat and blood samples were obtained from 10 dairy cows 1 week before and 3 weeks after calving. For AdipoR1 and AdipoR2 mRNA abundance as well as for leptin concentrations in plasma, a reduction (P ≤ .05) was observed postpartum; for visfatin and putative GPR 109A mRNA abundance in adipose tissue, there was a trend (P < .1) for analogous changes. In contrast, the mRNA content of obRb and GPR 41 in adipose tissue was higher (P ≤ .05) in samples from early lactation than in those from late gestation. Our results indicate decreasing adiponectin sensitivity in adipose tissue after calving, which might be involved in the reduced insulin sensitivity of adipose tissue during early lactation. In addition, visfatin, GPR 41, and GPR 109A may further modulate insulin sensitivity.     

Bactrian camel (Camelus bactrianus) integrins αvβ3 and αvβ6 as FMDV receptors: Molecular cloning, sequence analysis and comparison with other species

Integrins are heterodimeric adhesion receptors that participate in a variety of cell–cell and cell–extracellular matrix protein interactions. Many integrins recognize RGD sequences displayed on extracellular matrix proteins and the exposed loops of viral capsid proteins. Four members of the αv integrin family of cellular receptors, αvβ3, αvβ6, αvβ1 and αvβ8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro, and integrins are believed to be the receptors used to target epithelial cells in the infected animals. To analyse the roles of the αv integrins from a susceptible species as viral receptors, we have cloned Bactrian camel αv, β3 and β6 integrin cDNAs and compared them to those of other species. The coding sequences for Bactrian camel integrin αv, β3 and β6 were found to be 3165, 2289 and 2367 nucleotides in length, encoding 1054, 762 and 788 amino acids, respectively. The Bactrian camel αv, β3 and β6 subunits share many structural features with homologues of other species, including the ligand binding domain and cysteine-rich region. Phylogenetic trees and similarity analyses showed the close relationships of integrin genes from Bactrian camels, pigs and cattle, which are each susceptible to FMDV infection, that were distinct from the orders Rodentia, Primates, Perissodactyla, Carnivora, Galliformes and Xenopus. We postulate that host tropism of FMDV may in part be related to the divergence in integrin subunits among different species.     

Immunomodulatory effects of β-glucans on porcine alveolar macrophages and bone marrow haematopoietic cell-derived dendritic cells

The immunopharmacological activities of β-glucans with a backbone of β-1,3/β-1,6-linkages associated with anti-tumor, anti-viral, bacterial and fungal infections have been well documented. Dectin-1, a specific pattern recognition receptor for β-1,3/β-1,6-glucans, is expressed mainly on phagocytes, especially macrophages and dendritic cells (DCs). In this study, the encoding nucleotide for the carbohydrate-recognition domain (CRD) of porcine dectin-1 was sequenced for the first time, and the immunomodulatory functions of a synthetic particulate β-glucan (p-β-glucan) were examined. Results showed that p-β-glucan significantly enhanced cell activity and phagocytosis in porcine alveolar macrophages (AMs), immature DCs (imDCs) and mature DCs (mDCs), in a similar way to zymosan. Zymosan enhanced dectin-1/TLR2/TLR4 expression and TNF-α/IL-10 production in all of three types of cell, whereas p-β-glucan increased dectin-1/TLR4 and TNF-α/IL-12 production in AMs but inhibited IL-10 in mDCs. These results indicate that the complex collaborating interactions between dectin-1 and TLRs in the recognition of β-1,3/β-1,6-glucans with different structural features may direct different cellular responses.