Objective
To discuss the role of heparan sulfate (HS) in bone formation and bone remodeling and summarize the research progress in the osteogenic mechanism of HS.
Methods
The domestic and abroad related literature about HS acting on osteoblast cell line in vitro, HS and HS composite scaffold materials acting on the ani-mal bone defect models, and the effect of HS proteoglycans on bone development were summarized and analyzed.
Results
Many growth factors involved in fracture healing especially heparin-binding growth factors, such as fibroblast growth factors, bone morphogenetic protein, and transforming growth factor β, are connected noncovalently with long HS chains. HS proteoglycans protect these proteins from protease degradation and are directly involved in the regulation of growth factors signaling and bone cell function. HS can promote the differentiation of stem cells into osteoblasts and enhance the differentiation of osteoblasts. In bone matrix, HS plays a significant role in promoting the formation, maintaining the stability, and accelerating the mineralization.
Conclusion
The osteogenesis of HS is pronounced. HS is likely to become the clinical treatment measures of fracture nonunion or delayed union, and is expected to provide more choices for bone tissue engineering with identification of its long-term safety.
ObjectiveTo summarize the latest progress of microRNA (miRNA or miR) in colorectal cancer (CRC)-related signaling pathways in the past three years, and provide new ideas for miRNA-targeted intervention or miRNA as tumor molecular markers for early diagnosis of CRC. MethodThe literature on the roles of miRNA in the CRC-related signaling pathways was retrieved and reviewed. ResultsMiRNAs were associated with cancers in nearly all critical pathways, which regulated almost all important signaling pathways associated with CRC. At present, the signaling pathways and miRNAs related to CRC mainly included Wnt-β-catenin (miR-520e, miR-8063, miR-576-5p, miR-142-3p, miR-19a-3p, miR-381, miR-411, miR-1205), phosphatidylinositol-3-kinaset-Akt (miR-19a, miR-493-5p, miR-3064-5p, mi-196b-5p, miR-3651), mitogen-activated protein kinase (miR-1288-3p, miR-3651, miR-152-3p), transforming growth factor-β (miR-183-5p, miR-21-5p, miR-195-5p, miR-581, miR-2911, miR-128-3p, let-7a), nuclear factor kappa B (miR-155, miR-129, miR-21), Janus kinase/signal transducers and activators of transcription (miR-198, miR-452, miR-128-3p, miR-495), Notch (miR-223, miR-10b, miR-449a), Hippo (miR-30a-5p, miR-375, miR-9), and Hedgehog (miR-372, miR-373), etc. signaling pathways. ConclusionsMiRNA play a role in one or more signaling pathways at the same time, and play an important regulatory role in the occurrence and development of CRC. MiRNAs have great potential as tumor markers in the diagnosis, treatment, and prognosis of colorectal cancer.
ObjectiveTo summarize the latest research progress of graphene and its derivatives (GDs) in bone repair. MethodsThe relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed. ResultsThe application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior.ConclusionGDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.
The gut mucus barrier and mechanical barrier are the most important natural barriers, the former is the first defense barrier, which separates pathogenic bacteria in intestinal lumen from the epithelial cells, and prevents them passing through the intestinal barrier into the human circulation system. Studies have shown that inflammation in the body affects the content of mucin 2, a key protein in the mucus layer, thereby changing the permeability of the mucus barrier and promoting the translocation of pathogenic microorganisms. Both tumor necrosis factor-α and c-jun N-terminal kinase signaling pathways have been reported to be closely related to the occurrence and development of inflammation. Therefore, this article reviews the relationship between tumor necrosis factor-α, c-jun N-terminal kinase signaling pathway and mucin 2 and intestinal barrier dysfunction, in order to provide new ideas and directions for exploring the related research of intestinal barrier function.
Objective
To investigate the expression of neutrophil gelatinase-associated lipocalin (NGAL) signaling pathways in the early stage of porcine vein graft restenosis, and to explore the possible role and mechanism in the early vein graftrestenosis after coronary artery bypass surgery.
Methods
We selected 18 ordinary healthy pigs weighing 25-30 kg and collected samples of the vein graft of pigs at the preoperation and postoperative days 7, 14 and 30. Hematoxylin-eosin (HE) staining and Masson staining, immunohistochemical method were used to observe the neointimal hyperplasia, the migration of smooth muscle cells and and vascular remodeling of the vein bypass graft. The expression changes of NGAL, matrix metalloprotenase (MMP)9, MMP2 and tissue inhibitor of metalloproteinase (TIMP)1 in different periods of the vein bypass graft was tested.
Results
By HE and Masson staining, with the passing of modeling time, degradation of collagen matrix in the vein graft, gradually thickening of muscle fibers and the migration to the inner membrance and vascular remodeling caused the vascular stenosis. By immunohistochemistry, NGAL, MMP9 and MMP2 of normal vein in the model were seldom expressed and even did not express. At 14 days after the modeling, NGAL expression in the membrane layer of blood vessels began to appear, peaked at postoperative 30 days, and began to appear in the inner membrance. MMP9, MMP2 expression began to appear at postoperative 7 days, peaked at postoperative 14 days, and tended to decline at postoperative 30 days. TIMP1 expression was less in normal vascular walls and at the 14 days after the modeling, expression peaked in the vein graft.
Conclusion
NGAL, MMP9, MMP2 and TIMP1 may be involved in the formation of early vascular graft restenosis. NGAL as initiator, results in the expression of MMP9 and MMP2, and participates in the degradation of collagen matrix and the migration of smooth muscle cells in vein grafts. TIMP1 as a negative factor, may play an important role in maintaining their own balance.
After the articular cartilage injury, the metabolic level is increased during the progressive degeneration, the chondrocytes secrete a variety of inflammatory factors, and the original cell phenotype is gradually changed. For a long time, a large number of researchers have done a lot of researches to promote anabolism of chondrocytes and to maintain the stability of chondrocyte phenotype. There are many molecular signaling pathways involved in the process of promoting cartilage repair. This review focuses on the key signaling molecules in articular cartilage repair, such as transforming growth factor-beta and bone morphogenetic protein, and reveals their roles in the process of cartilage injury and repair, so that researchers in related fields can understand the molecular mechanism of cartilage injury and repair widely and deeply. Based on this, they may find promising targets and biological methods for the treatment of cartilage injury.
A new independent subtype CD4+ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.
Rheumatoid arthritis (RA) is a chronic autoimmune disease remarkably characterized by synovitis of joints, whose pathogenesis is complicated and not yet fully elucidated. A variety of cells, cytokines and intercellular signaling pathways are involved in the occurrence and development of RA. The mitogen activation protein kinase (MAPK) signaling pathway is closely related to the pathogenesis of RA, and plays an important role in the formation of pannus, synovitis, and bone destruction. This paper reviews the research progress of MAPK signaling pathway in RA from the aspects of the interaction of MAPK signaling pathway with a variety of key cells and cytokines in the pathogenesis of RA, in order to provide a direction and theoretical basis for anti-RA drug therapy research.
Objective To investigate the structure characteristics， functions， and research progress of Notch signaling pathway in digestive tumors. Methods The related literatures about the molecular genetic mechanism of Notch signaling pathway were reviewed. Results The Notch signaling pathway plays an important role not only in normal cells’ growth， differentiation， proliferation， and apoptosis but also in a variety of tumors’ occurrence and development. Conclusion The reasonable regulation to Notch signaling pathway may open up new ways to the treatment of the tumor.
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
