Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis.

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.

[A medium term analysis on of therapeutic effects of bio-lengthend stem hemiarthroplasty in the treatment of unstable osteoporotic intertrochanteric fractures in elderly patients].

OBJECTIVE: To retrospectively study medium term follow up outcomes effects of effect of bio-lengthend stem hemiarthroplasty in the treatment of unstable osteoporotic intertrochanteric fractures in elderly patients. METHODS: Total of 32 elderly patients with the osteoporotic intertrochanteric fractures were treated with bio-lengthend stem hemiarthroplasty from Jan. 2016 to Jan. 2019 including 14 males and 22 females, aged from 85 to 95 years old with an average of (89.5±4.5) years old. According to classification of Evans, there were 12 cases with type Ⅲ, 11 with type Ⅳ and 9 with type Ⅳ. The time from injury to operation ranged from 0.5 to 9 days with an average of (4.5±3.9) days. The operation time, blood loss and postoperative complications were analyzed. Functional outcome was assessed by Parker Palmer mobility score(PPMS) and Harris hip score. RESULTS: Four patients died within one year after operation, and the mortality was 12.5%. The follow up time for the rest 28 patients ranged from 24 to 60 months with an average of (28.5±4.5) months. The mean operative time was (54.2±22.5) min;the mean blood loss (hidden blood loss+obvious blood loss) was (450±140) ml;the first weight bearing was (3.35±1.35) days. No perioperative death occurred. PPMS were(6.63±1.25), (6.94±1.18), (7.11±0.83), (7.32±1.11) and Harris scores were(67.85±6.19), (71.42±5.57), (73.41±5.62), (77.32±5.24) respectively at 1, 3, 6 months and the final follow-up after operation. There were no significant difference in PPMS and Harris score at 1, 3, 6 months after operation and the final follow-up(P>0.05). There were no complications such as joint dislocation and prosthesis loosening occure at the final follow-up. CONCLUSION: On the premise of strictly mastering the case selection criteria, the bio-lengthend stem hemiarthroplasty in the treatment of unstable osteoporotic intertrochanteric fractures in elderly patients has a satisfied medium term follow-up outcomes. It can restore hip function in the early stage and improve the quality of life of patients.

Network Pharmacology-Based Prediction and Verification of the Potential Targets of Pinoresinol Diglucoside for OA Treatment.

Objective: This study aimed to explore the effects and related mechanisms of pinoresinol diglucoside (PDG) on osteoarthritis (OA) via a combination of pharmacology and animal experiments. Methods: Traditional Chinese Medicine Database and Analysis Platform (TCMSP) Drugbank, Online Mendelian Inheritance in Man, and GeneCards databases were used to predict the putative targets of PGD against OA. A protein protein interaction (PPI) network was constructed in STING database to analyze the interaction network of these targets. Enrichment analysis was performed with DAVID database. The OA model was built by anterior cruciate ligament transection and then injected with PDG for 5 weeks. Hematoxylin and eosin (HE) staining and safranin-fixed green staining were used to evaluate the pathological change. ELISA was applied to measure the serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Immunohistochemistry was employed to detect the protein levels of kinase B (AKT), BAX, Bcl2, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and phosphatidylinositol 3 kinase (PI3K) in knee cartilage tissues. Results: Seventy-one key targets were identified, including AKT1, epidermal growth factor receptor, SRC, estrogen receptor 1 (ESR1), and MMP9. Enrichment analysis revealed a series of pathway related to cancer, PI3K-Akt signaling pathway, and proteoglycans in cancer. Animal experiments showed that PDG alleviated the abnormal histomorphological changes of OA; suppressed TIPM, serum IL-1ß, IL-6, and TNF-α levels, and PI3K and AKT activation; and increased MMP-1 expression and Bcl2/Bax ratio. Conclusion: PDG has a cartilage-protecting effect associated with PI3K/AKT signaling pathway in rabbit with OA and therefore might serve as a potential agent for the treatment of this disease.