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Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).
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To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] ( values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the (95) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.
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OBJECTIVE@#To explore whether tumor suppressor gene Foxo1 and PTEN play a critical role in the tumorigenesis of mouse natural killer-cell lymphoma.@*METHODS@#NKp46-iCre mice were crossed with mice carrying floxed Foxo1 alleles (Foxo1) as well as floxed PTEN alleles (PTEN) to generate mice in which Foxo1 and PTEN in NK cells were knock-out, referred as Foxo1PTEN. The growth and development of the mice and tumor formation were observed. The flow cytometry was used to detect the percentages of NK cells in main lymphatic organs. B16F10 metanoma model of tumor metastasis was utilized to investigate NK cell-mediated tumor surveillance in vivo after NK cells special deletion of Foxol and PTEN.@*RESULTS@#The mouse model with NK cell-special Foxo1 and PTEN double knockout was established. Compared with control group (Foxo1PTEN mice), Foxo1PTEN mice were born alive and appeared to be healthy over a period of 46 weeks. No spontaneous tumor formation was observed at this stage. There were no significant differences in NK cell percentages of gated lymphocytes from various organs including blood, bone marrow, peripheral lymph node and spleen between Foxo1PTEN mice and Foxo1PTEN mice [PB: 4.76%±0.46% vs 4.17%±0.64% (P＞0.05, n=8); BM: 1.13%±0.23% vs 1.31%±0.10% (P＞0.05, n=8) ; LN: 0.50%±0.10% vs 0.85%±0.20% (P＞0.05, n=8); SP: 4.41%±0.65% vs 3.50%±0.24% (P＞0.05, n=8)]. B16F10 melanoma metastasis model of tumor was established, No differences in median survival time were observed in the 2 types of mice (P＞0.05, n=13).@*CONCLUSION@#The simultaneous deletion of the Foxo1 and PTEN genes may not plays significant role in the tumorigenesis of mouse natural killer-cell lymphoma and NK cell-mediated tumor surveillance in vivo.
Subject(s)
Animals , Mice , Cell Transformation, Neoplastic , Forkhead Box Protein O1 , Genes, Tumor Suppressor , Killer Cells, Natural , Lymphoma , Mice, KnockoutABSTRACT
@#Systematic lymph nodes dissection has been a standard procedure in lung cancer surgery, while the manipulation of mediastinal lymph nodes for early stage lung cancer remains controversial since surgeons have been weighing the advantages and disadvantages of different methods of lymph node dissection. With an increasing in early stage non-small cell lung cancer patients in recent years, there are more and more intensive studies especially focusing on the mediastinal lymph nodes dissection of clinical stage ⅠA lung cancer. In this review, the lymph nodes management of clinical stage ⅠA non-small cell lung cancer, especially systematic lymph nodes dissection and sampling as well as lobespecific lymph node dissection, are summarized.
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<p><b>OBJECTIVE</b>To investigate the possibility to enhance the proliferation of adipose-derived stem cells (ASCs) in a delayed fat flap in rabbits.</p><p><b>METHODS</b>A delayed fat flap was formed in one side of inguinal region of a rabbit. 21 days after operation, the fat tissues at the delayed flaps and at the unoperated side were harvested and digested with 0.25% collagenase and sieved. The cell suspensions were centrifuged. The cells were obtained from tissue precipitate after centrifugation. The expression rates of the surface marker (CD29, CD44, CD14 and CD45) were measured by FCM and compared between the experimental and control groups.</p><p><b>RESULTS</b>Expression rates of CD29 and CD44 were higher in the delayed fat flap (74.06% and 90.74%) than in the contralateral fat tissue (62.88% and 77.54%, P < 0.05), while those of CD14 and CD45 were lower in the delayed fat flap (57.66% and 4.84%) than in the contralateral fat tissue (72.10% and 75.82%, P < 0.05 and P < 0.01).</p><p><b>CONCLUSIONS</b>Tissue hypoxic ischemia such as fat tissue in a delayed fat flap can promote proliferation of ASCs. It indicates that tissue in the delayed flap may be transplanted with better survival rate. The ischemia pretreatment of fat tissue may become a new method for fat transplantation.</p>
Subject(s)
Animals , Rabbits , Adipose Tissue , Cell Biology , Transplantation , Cell Proliferation , Cells, Cultured , Graft Survival , Postoperative Period , Stem Cells , Cell Biology , Surgical FlapsABSTRACT
Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. C2- ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the C2-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited C2-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the C2- ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit C2-ceramide induced contraction via PKC and MAPK dependent pathway.