Myeloid-derived suppressor cells (MDSCs),a heterogeneous population of immature myeloid cells,play an important role in immune tolerance and immune suppression.In recent years,more and more research results show that the prostaglandin E2 (PGE2) has an inseparable relationship with MDSCs,and PGE2 through its relevant receptors,regulating signal transducer and activator of transcription 3 (STAT3) and protein kinase A cell signaling pathways and secretion cytokines in tumor microenvironment,affects the development,differentiation and function of MDSCs.

OBJECTIVETo investigate the effects of icariin on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats.

METHODMale SD rats were randomly divided into normal control group, icariin control group, diabetic group, and diabetic groups administered with a low dose (30 mL x kg(-1) x d(-1), ig) or a high dose (120 mL x kg(-1) d(-1), ig) of icariin for 8 weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, and myocardial collagen level were assayed. The cardiac mitochondrial reactive oxygen species (ROS) level, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured.

RESULTTreatment with icariin reduced the losing of body weight in diabetic rats. Icariin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure and +/- dp/dt(max), and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial collagen and the level of cardiac mitochondrial ROS in diabetic rats were all markedly reduced by icariin. Furthermore, high dose of icariin significantly decreased the mitochondrial MDA level and increased SOD activity in diabetic rat hearts.

CONCLUSIONTreatment with icariin for 8 weeks markedly improved the cardiac function, which may be related to reducing mitochondrial oxidative stress injuries in diabetic rats.

Animals ; Body Weight ; drug effects ; Collagen ; drug effects ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; metabolism ; pathology ; Diabetes Mellitus, Type 1 ; drug therapy ; metabolism ; pathology ; Diabetic Cardiomyopathies ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Enteral Nutrition ; Flavonoids ; administration & dosage ; Heart Ventricles ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Heart ; drug effects ; metabolism ; pathology ; Organ Size ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Streptozocin ; Superoxide Dismutase ; drug effects ; metabolism

BACKGROUND:Silk fibroin, as a kind of high-performance biomaterial, has been widely used to construct scaffolds in bone tissue engineering. However, whether silk fibroin itself holds osteoinductive ability has not been reported yet. OBJECTIVE:To investigate the impact of different concentrations of silk fibroin solution on the proliferation and differentiation of rat bone marrow mesenchymal stem cel s (BMSCs) in vitro. METHODS:Silk fibroin and BMSCs were respectively isolated from silkworm cocoon and rat tibia, and were identified. Then, BMSCs were cultured in different concentrations of silk fibroin solution (0.01%, 0.05%and 0.1%), and the cell proliferation and the alkaline phosphatase activity were detected at different time points. RESULTS AND CONCLUSION:FTIR spectra of the sample extracted from silkworm cocoon showed distinct absorption peaks at 1 653 (amide I), 1 530.5 (amide II) and 1 212.3 cm-1 (amide III), which could be confirmed to be silk fibroin. Thus generated BMSCs showed long fusiform or astral morphology, positive for representative markers (CD29, CD44 and CD90) relating to mesenchymal stem cells, and could differentiate into osteocytes, chondrocytes and adipocytes under specific induction conditions, which further confirmed the extracted cells were BMSCs. Compared with the control group (without silk fibroin), 0.05% silk fibroin not only significantly promoted the cell adhesion, migration and proliferation, but also enhanced the alkaline phosphatase activity (P<0.01). With the increasing of the silk fibroin concentrations, the osteodifferentiation capacity of the BMSCs was progressively improved within the range of 0-0.05%and then declined at 0.01%of silk fibroin solutions. These results suggest that silk fibroin can promote osteogenesis, thus providing scientific evidence for developing silk fibroin-based tissue-engineered scaffolds.

Objective To investigate the role of triggering receptor expressed on myeloid cells 1 (TREM1)in rats with neuropathic pain and its possible mechanism.Methods Forty-eight male a-dult Sprague-Dawley rats,weighing 220-300 g,were successfully placed intrathecal catheters,and then randomly divided into 4 groups (n=1 2 ):sham operation group (group S),neuropathic pain group (group CCI),TREM1 shRNA group (group RNAi)and negative lentivirus group (group Vi-rus).The neuropathic pain was induced by chronic sciatic nerve compression injury (CCI).In group RNAi,30 μl pGLVU6/RFP/Puro-shRNA (1×109IU/ml)was injected intrathecally 1 week before modeling.Group Virus was injected with 30 μl negative lentivirus,whereas group CCI and group S with equal amount of normal saline.MWT and TWL were measured 1 day before (baseline)and 1,3, 7,14 day after modeling.When behavioral test finished,the expression levels of TREM1,TLR4, MyD88,IκBαand p-NF-κB p65 in spinal cord were determined by Western blot.Whereas the mRNA expression levels of IL-1β,TNF-αand IL-6 in spinal cord were measured by RT-PCR.Results Com-pared with group S,the expression levels of TREM1 in groups CCI and Virus significantly increased (P<0.05).While compared with group CCI,the TREM1 expression of group RNAi in spinal cord significantly decreased (P<0.05).Compared with group S,MWT and TWL of groups CCI,Virus and RNAi after modeling and the expression of IκBαsignificantly decreased (P<0.05),whereas the expression of TLR4,MyD88,p-NF-κB p65 increased significantly (P<0.05),as well as the expres-sion of IL-1β,TNFαand IL-6 mRNA (P<0.05).Compared with group CCI,the MWT and TWL of group RNAi after modeling and the expression of IκBαremarkably increased (P<0.05),whereas the expression of TLR4,MyD88 and p-NF-κB p65 in the spinal cord remarkably decreased (P<0.05), as well as the expression of IL-1β,TNF-αand IL-6 mRNA (P<0.05).Conclusion TREM1 knock-down can alleviate neuropathic pain,the underlying mechanism might be the inhibition of TLR4/MyD88/NF-κB signaling pathway.