The effect of neutrophil extracellular traps (NETs) on promoting intravascular microthrombi formation and exacerbating the severity of sepsis in patients has gained extensive attention. However, in sepsis, the mechanisms and key signaling molecules mediating NET formation during direct interactions of endothelial cells and neutrophils still need further explored. Herein, we utilized lipoteichoic acid (LTA), a component shared by Gram-positive bacteria, to induce NET extrusion from neutrophils firmly adhered to the glass slides coated with intercellular adhesion molecule-1(ICAM-1). We also used Sytox green to label NET-DNA and Flou-4 AM as the intracellular Ca2+ signaling indicator to observe the NET formation and fluctuation of Ca2+ signaling. Our results illustrated that LTA was able to induce NET release from neutrophils firmly attached to ICAM-1-coated glass slides, and the process was time-dependent. In addition, our study indicated that LTA-induced NET release by neutrophils stably adhered to ICAM-1 depended on Ca2+ signaling but not intracellular reactive oxygen species (ROS). This study reveals NET formation mediated by direct interactions between endothelial ICAM-1 and neutrophils under LTA stimulation and key signaling molecules involved, providing the theoretical basis for medicine development and clinical treatment for related diseases.
Objective To summarize the relationship between tumor necrosis factor receptor-associated factor 6 （TRAF6） and apoptosis. Methods Domestic and international researches on progress of TRAF6 and apoptotic signaling pathway， especially focused on the functional features of TRAF6 in different system diseases were searched and reviewed. Results TRAF6 took part in several signaling pathways， which had been implicated in regulating apoptosis， and its roles differed in different system diseases and in different conditions. TRAF6 promoted tumorigenesis by inhibiting apoptosis， while it played a proapoptotic or prosurvival role in nervous system and inflammatory diseases. Conclusion TRAF6 plays an important role in apoptosis and involves in the development of tumor， nervous system disease， and inflammatory diseases.
ObjectiveTo review the research progress of microenvironment for the treatment of peripheral nervous injuries. MethodsThe recent literature concerning the treatment mechanism of peripheral nervous injuries was extensively consulted, and the microenvironment response involved in the treatment of peripheral nervous injuries was reviewed. ResultsThe complex microenvironment for treatment of peripheral nervous injuries is dependent on nerve regeneration chamber, the formation of neurotrophic factors, inflammation response, regulation of hormones, signaling pathways, and related enzymes in regulation. In-depth study will help us have a clearer understanding on the distal and proximal neurons axons at the cellular and molecular levels after peripheral nervous injuries. ConclusionIn recent years, the researches of microenvironment for the treatment of peripheral nervous injuries have achieved obvious progress. With the current nanotechnology, materials science, genetic engineering, and stem cell transplantation technology, it will provide new ideas and corresponding basis for clinical treatment.
ObjectiveTo review the mechanism and research progress of signal ing pathways which play key roles in the regulation of osteoblast differentiation and bone formation. MethodsRecent articles about signal ing pathways of osteoblast differentiation and bone formation were reviewed and comprehensively analyzed. ResultsAt present, multi ple signaling pathways have been found to be involved in the regulation of osteoblast differentiation and bone formation, among which bone morphogenetic protein-Smads, Wnt/β-catenin, Notch, Hedgehog, and fibroblast growth factor signaling pathways may play the most important roles. Not only each pathway has a complex regulatory mechanism itself, but also contacts and impacts with each other, thus they formed a more compl icated and sophisticated regulatory network, and regulate together osteoblast differentiation and bone formation. However, the mechanisms in detail of those pathways are still not very clear, because the animal experiment techniques are not yet mature as well as the relevant cl inical trials were carried out not too much. ConclusionThe complete molecular mechanism of osteoblast differentiation and bone formation should be further investigated, so as to lay a theory foundation for preventing and treating the common bone diseases in cl inical which are involve in osteoblast differentiation and bone formation.
ObjectiveTo detect FoxM1 expression in thyroid papillary carcinoma TPC-1 cells,and explore influence of FoxM1 expression on important genes (RAS gene and CDK1 gene) of mitogen activated protein kinase (MAPK) signal pathway. MethodsThe hFoxM1-RNA interference was used to deal with the thyroid papillary carcinoma TPC-1 cells (experiment group),another untreated TPC-1 cell was as control group.Then the real-time quantitative PCR was used to detect the FoxM1,Ras,and CDK1 gene expressions in all the TPC-1 cells. ResultCompared with the control group,the FoxM1 gene expression was significantly decreased (0.452 9 versus 1.005 0,t=24.692 9,P<0.01),the Ras gene expression was significantly elevated (1.319 0 versus 1.001 2,t=14.218 5,P<0.01),and the CDK1 gene expression was significantly decreased (0.767 5 versus 1.008 1，t=10.763 4,P<0.01) in the experiment group. ConclusionFoxM1 gene expression level in thyroid papillary carcinoma TPC-1 cells could influence Ras and CDK1 expression,which suggests that its role in thyroid papillary carcinoma might be associated with MAPK signal pathway.
Extracellular vesicles (EVs), defined as cell-secreted nanoscale vesicles that carry bioactive molecules, have emerged as a promising therapeutic strategy in tumor and tissue regeneration. Their potential in repairing intervertebral disc degeneration (IDD) through multidimensional regulatory mechanisms is a rapidly advancing field of research. This paper provided an overview of the mechanisms of EVs in IDD repair, thoroughly reviewed recent literature on EVs for IDD, domestically and internationally, and summarized their therapeutic mechanisms. In IDD repair, EVs could act through different mechanisms at the molecular, cellular, and tissue levels. At the molecular level, EVs could treat IDD by inhibiting inflammatory reactions, suppressing oxidative stress, and regulating the synthesis and decomposition of extracellular matrix. At the cellular level, EVs could treat IDD by inhibiting cellular pyroptosis, ferroptosis, and apoptosis and promoting cell proliferation and differentiation. At the tissue level, EVs could treat IDD by inhibiting neovascularization. EVs have a strong potential for clinical application in the treatment of IDD and deserve more profound study.
ObjectiveTo summarize the research progress of yes association protein (YAP) mechanisms regulatedby different signaling pathways in tumor cells in recent years. MethodsLiteratures about the recent studies on the YAP mechanisms regulated by different signaling pathways in tumor cells were reviewed according to the results searched from PubMed database. ResultsIn addition to the traditional HIPPO pathway for the regulation of YAP, YAP is also regulated by the Rho-GTPases, JNK, and Wnt/β-Catenin signal pathways. ConclusionYAP is regulated by many factors in tumor cells, so better understand the mechanisms of YAP regulated by different signaling pathways will provide anovel putative target fortumor diagnosis and therapy in the future.
ObjectiveTo explore if Smad7 protein can inhibit growth of keloids by observing the gene and protein expressions of Smad7, collagen type Ⅰ, and collagen type Ⅲ and cell proliferation after over-expression vectors of Smad7 transfecting keloid fibroblasts (KFb). MethodsFibroblasts were acquired from 10 male patient with keloids at the age of 20 to 25 years. After in vitro culture, KFb were divided into 3 groups: untransfected group (group A), pcDNA3.1 (-) transfected group (group B), and pcDNA3.1 (-)-smad7 transfected group (group C). The mRNA and protein expression levels of Smad7, collagen type Ⅰ, and collagen type Ⅲ were detected by real-time fluorescence quantitative PCR and Western blot at 48 hours after transfection. The cell proliferation ability was detected by MTT assay at 24 hours after transfection. ResultsThe relative expression levels of mRNA and protein of Smad7 in group C were significantly higher than those in group A and group B (P < 0.01). The relative expression levels of mRNA and protein of collagen type Ⅰ and collagen type Ⅲ in group C were significantly lower than those in group A and group B (P < 0.01). The relative expression levels of mRNA of collagen type Ⅰ and collagen type Ⅲ in group B were significantly higher than those in group A (P < 0.01); and the relative expression levels of proteins of Smad7, collagen type Ⅰ, and collagen type Ⅲ were significantly lower than those in group A (P < 0.01). The cell proliferation ability in group C was significantly lower than that in group A and group B at each time point by MTT assay (P < 0.05), but no difference was found between group A and group B (P>0.05). ConclusionGene expressions of collagen type Ⅰ, and collagen type Ⅲ and cell proliferation will be inhibited after KFb are transfected by over-expression vector of Smad7.
Objective To review the latest development of the research on the selfrenwal signaling pathway and culture system in vitro of the embryonic stem cells(ESCs). Methods The recent articlesabout the selfrenewal signaling pathway and culture system in vitro of the ESCs were extensively reviewed. Results Understanding of the molecular mechanism of the selfrenewalin vitro and pluripotency of the ESCs was considered important for developing improved methods of deriving, culturing and differentiating these cells into the cells that could be successfully used in the clinical practice. Conclusion A further research is needed to elucidate the selfrenewal signaling pathway and the pluripotency of the ESCs and the culture systemin vitro forthe human ESCs remains to be further improved and developed.
ObjectiveTo investigate the effects of signaling pathway about the EGFR, MAPK, IKB/NF-κB, PI3K/Akt, WNT/beta-catenin, and the Hedgehog in development of hepatocellular carcinoma(HCC). MethodsThe related literatures about the molecular genetic mechanism of signaling pathways were reviewed. ResultsIn the occurrence and development of HCC, the EGFR, MAPK, IKB/NF-κB, PI3K/Akt, WNT/β-catenin, and Hedgehog signaling pathways not only interweaver with each other complexly, but also interact with each other, and some tumor markers, anticancer genes, proto-oncogenes, and miRNA may have synergistic effects for the occurrence of HCC. ConclusionThe abnormal changes of molecular signaling pathways is a necessary condition for the occurrence and development of tumor, and there is considerable cross-talk and redundancy to many signaling pathways.