RESUMEN
Postmenopausal osteoporosis (PMOP) has become one of most frequent bone diseases worldwide with aging population. Lycii Fructus, a common plant fruit with the property of drug homologous food, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of Lycii Fructus against PMOP through using network pharmacology approach. The active ingredients of Lycii Fructus were obtained from Traditional Chinese Medicine System Pharmacology database. Target fishing was performed on these ingredients in UniProt database for identification of the relative targets. Then, we screened the targets related to PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and Lycii Fructus were obtained to perform protein-protein interaction, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis. A total of 35 active ingredients were identified in Lycii Fructus, and fished 158 related targets. Simultaneously, 292 targets associated with PMOP were obtained from GeneCards database and DisGeNET database. By drawing Venn diagram, 41 overlapping genes were obtained, and were considered as therapeutically relevant. Gene ontology enrichment analysis predicted that anti-inflammation and promotion of angiogenesis might be 2 potential mechanism of Lycii Fructus for PMOP treatment. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as IL-17 pathway, TNF pathway, MAPK pathway, PI3K-Akt signaling pathway and HIF signaling pathway were involved in regulating these 2 biological processes. Through the method of network pharmacology, we systematically investigated the mechanisms of Lycii Fructus against PMOP. The identified multi-targets and multi-pathways provide new insights to further determinate its exact pharmacological mechanisms.
Asunto(s)
Enfermedades Óseas , Medicamentos Herbarios Chinos , Osteoporosis Posmenopáusica , Humanos , Femenino , Anciano , Osteoporosis Posmenopáusica/tratamiento farmacológico , Frutas , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Through the network pharmacology thought, the action target of the active ingredients of Drynariae Rhizoma was predicted, and the mapping was combined with the related targets of ONFH, and the key nodes of interaction were identified for enrichment analysis, so as to comprehensively explore the pharmacological mechanism of Drynariae Rhizoma against ONFH. The main active ingredients of Drynariae Rhizoma were screened based on pharmacokinetic characteristics in pharmacokinetic database and analysis platform of TCM system (TCMSP). We used the organic small molecule bioactivity database (PubChem) and Swiss target prediction database to predict related targets based on 2D or 3D structural similarity and then mined the known ONFH therapeutic targets through the Human Mendelian Genetic Database (OMIM) and Pubmed texts. Combined with the predicted targets, String database was imported to construct the OP target interaction network diagram of bone fracture therapy. CytoNCA software was used to topology the key nodes of interaction according to relevant node parameters, and String was imported again to construct the protein interaction network diagram. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. It was revealed that Drynariae Rhizoma may regulate stem cells, osteoblasts, osteoclasts, and immune cells through multiple pathways, including proliferation, differentiation, immunity, and oxidative stress. Conclusion: Pharmacological studies based on network indicate that Drynariae Rhizoma may participate in the regulation of several major signaling pathways through direct or indirect action targets and affect the proliferation and differentiation of multiple types of cells, thus playing an anti-ONFH role, which provides a scientific basis for explaining the material basis and mechanism of its anti- ONFH.
Asunto(s)
Medicamentos Herbarios Chinos , Necrosis de la Cabeza Femoral , Polypodiaceae , Medicamentos Herbarios Chinos/farmacología , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Polypodiaceae/química , Rizoma/químicaRESUMEN
BACKGROUND: Wound healing is an essential physiological process in recovery after microsurgery. OBJECTIVES: To further understand the functions of fibroblast growth factor 21 (FGF21), the roles of this factor were examined and its correlations with inflammation, vascular endothelial growth factor A (VEGFA) and ERK1/2 signaling pathway activation were analyzed. MATERIAL AND METHODS: Rat brain microvascular endothelial cells (RBMECs) were treated with interleukin (IL)-1ß and used for the experiments. Cell Counting Kit-8 (CCK-8) was used to detect the cell viability of RBMECs after treatment with IL-1ß (1 ng/mL) and FGF21 or VEGFA overexpression, while changes in apoptosis were measured through flow cytometry. Migration was checked through the scratch test. FGF21 and VEGFA RNA expression was assessed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), which was also used to examine RNA expression of Bcl-2, Bax and caspase-3. After IL-1ß treatment and FGF21 overexpression, tumor necrosis factor alpha (TNF-α) and tumor growth factor ß1 (TGF-ß1) proteins level were observed with enzyme-linked immunosorbent assay (ELISA), which was also applied to check the expression of ERK1/2 after overexpression of FGF21 and VEGFA. PD98059 (50 µM), an ERK1/2 inhibitor, was used to examine the roles of ERK1/2 in regulating cell viability and apoptosis. RESULTS: The IL-1ß treatment significantly decreased the viability of RBMECs and TGF-ß1, but promoted cell apoptosis and TNF-α expression. FGF21 was downregulated by IL-1ß treatment but its overexpression enhanced the viability of RBMECs and TGF-ß1 and ERK1/2 protein levels, and attenuated cell apoptosis and TNF-α. Upregulated TNF-α restrained cell viability and apoptosis of RBMECs after FGF21 overexpression, and its upregulation not only suppressed FGF21, but also VEGFA. Moreover, VEGFA suppression by TNF-α increased cell viability and ERK1/2 protein levels, and suppressed the apoptosis of RBMECs through its upregulation. However, PD98059 obstructed the functions of FGF21 and VEGFA. CONCLUSIONS: FGF21 promoted the cell viability of RBMECs through upregulating TNF-α-mediated VEGFA and ERK1/2 signaling.
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Factor de Necrosis Tumoral alfa , Factor A de Crecimiento Endotelial Vascular , Animales , Apoptosis , Encéfalo , Células Endoteliales , Factores de Crecimiento de Fibroblastos , Sistema de Señalización de MAP Quinasas , Ratas , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Cicatrización de HeridasRESUMEN
BACKGROUND: The study aimed to confirm the important role of ozone autologous blood therapy (autohemotherapy) in promoting successful finger replantation and its possible influence mechanism. METHODS: A total of 150 patients with severed finger replantation admitted to our hospital from March 2018 to March 2019 were selected. Patients were divided into observation group and control group according to different treatment methods. The observation group received additional ozone autologous blood treatment in the control group. We compared the number of white blood cells, visual analogue scale (VAS) scores, and the expression levels of vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and platelet-derived growth factor (PDGF) in the two groups of patients before and after intervention. We also assessed the hospitalization time and survival time of the replanted finger in the two groups, as well as blood flow values (Vbcf). RESULTS: Compared with the observation group on the 1st day after the operation and the control group on the 7th day after the operation, the average white blood cell count of the observation group on the 7th day after the operation was significantly increased (P<0.05), and the VAS score was significantly decreased (P<0.05).48 hours after the operation, the average Vbcf value of the replanted finger was lower than that of the contralateral healthy finger (P<0.05). Compared with the control group, the Vbcf value of the replanted fingers in the observation group was higher, and the hospitalization time and finger survival time were shorter (P<0.05). At 7 days after operation, the serum VEGF, TGF-ß and PDGF levels in the observation group were significantly higher than the 1 day after operation, before the operation and the control group (P<0.05). CONCLUSIONS: Intervention with ozone autohemotherapy after severed finger replantation can significantly increase the number of white blood cells, relieve postoperative pain, and improve the survival rate of the finger body. Ozone autohemotherapy also improves the microcirculation after anastomosis of the severed finger by up-regulating the expression of VEGF, TGF-ß and PDGF in blood.
Asunto(s)
Dedos/cirugía , Ozono/uso terapéutico , Factor de Crecimiento Derivado de Plaquetas , Reimplantación , Factor de Crecimiento Transformador beta , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor de Crecimiento Transformador beta/sangre , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
OBJECTIVE: To investigate the mechanical characteristics of new anatomic plate of distal tibia from view of biomechanics. METHODS: Twelve fresh adult moist ankle specimens were randomly divided into four block groups (every group had 3 specimens), 3 tibial specimens as a normal control (normal group N), 9 specimens were resulted in unstable distal tibial Pilon fracture. Using steel plate fixation with a new anatomic distal tibial plate (group A), reconstruction plate (group B), clover plate (group C). Group B and group C as control group to test the remote axial compressive strength, remote axial stiffness, reversing biomechanical properties, contacted characteristics of the tibial astragaloid articular surface. RESULTS: The remote axial compressive strength, remote axial stiffness, reversing biomechanical properties, contacted characteristics of tibial astragaloid articular surface the in distal tibial Pilon fracture instability of group A were near normal group N (P>0.05). Group A was best than group B and C (P<0.05). CONCLUSION: The new anatomic plate of distal tibia was relatively strong, which can reach effective and stable fixation for unstable distal tibial Pilon fracture.