ABSTRACT
The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.
Subject(s)
Humans , Molecular Docking Simulation , Network Pharmacology , Osteogenesis , Phosphatidylinositol 3-Kinases , Osteoporosis , Databases, GeneticABSTRACT
To determine the potential of the high mobility group box-1 protein 1 (HMGB1) to activate Toll-like receptor 4 (TLR4) signaling in hepatic stellate cells (HSCs) and investigate the subsequent transition of HSC towards the inflammatory phenotype. Three immortalized mouse HSC cell lines, wild-type (JS1), TLR4-/- (JS2) and MyD88-/- (JS3), were subcultured in plates and divided into groups of normal control (untreated), postive control (lipopolysaccaride, LPS treatment), and experimental (HMGB1 treatment). All groups were transfected with luciferase reporter plasmids carrying responsive elements for either the nuclear factor-kappa B (NF-kB) or activator protein-1 AP-1 transcription factors. Following stimulation with normal saline, LPS (100 ng/mL) or HMGB1 (100 ng/mL), the activation of NF-kB or AP-1 was detected by a dual-luciferase reporter assay system. The induction of monocyte chemotactic protein-1 (MCP-1) transcription was determined by measuring the mRNA levels using real time quantitative reverse transcription PCR (qRT-PCR). The secreted protein levels of MCP-1 were determined by enzyme-linked immunosorbent assay (ELISA) of the culture supernatants. Activation of NF-kB- and AP-1-responsive reporters was significantly up-regulated in JS1 cells treated with HMGB1 or LPS, and the activation was coincident with markedly up-regulated transcription and secretion of MCP-1. However, HMGB1 and LPS treatment produced no responsive of the NF-kB and AP-1 reporters, and no increase in expression or secretion of MCP-1, in JS2 or JS3 cells. As an endogeous ligand of TLR4, HMGB1 may activate TLR4 signaling and the TLR4-mediated inflammatory response of HSC.
Subject(s)
Animals , Mice , Cell Line , Chemokine CCL2 , Genetics , Metabolism , Gene Knockout Techniques , HMGB1 Protein , Pharmacology , Hepatic Stellate Cells , Metabolism , Lipopolysaccharides , Pharmacology , NF-kappa B , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Signal Transduction , Toll-Like Receptor 4 , Genetics , Metabolism , Transcription Factor AP-1 , Genetics , Metabolism , Transfection , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical effect of subcutaneous undermining dissection with continuous negative pressure drainage for the closure of cystic cavity-type bedsore.</p><p><b>METHODS</b>12 patients with cystic cavity-type bedsore underwent surgical debridement and the wounds were closed after subcutaneous undermining dissection. The negative pressure drainage was put in the deep space. The healing process was observed.</p><p><b>RESULTS</b>Completed healing was achieved in all the 12 cases. The skin wounds healed after 17-20 days and the deep spaces closed after 36-43 days. 12 cases were followed up for 1 year with no occurrence.</p><p><b>CONCLUSIONS</b>It is an easy and effective method to treat cystic cavity -type bedsore by subcutaneous undermining dissection with continuous negative pressure drainage.</p>
Subject(s)
Humans , Debridement , Methods , Drainage , Methods , Negative-Pressure Wound Therapy , Pressure Ulcer , General Surgery , Wound HealingABSTRACT
<p><b>OBJECTIVE</b>To study the healing effect of pneumoconiosis with tetrandrine and massive whole-lung lavage.</p><p><b>METHODS</b>Choose 34 confirmed pneumoconiosis patients as drug treatment group and complex treatment group, and 17 tested workers as control group. Collected the content of TGF-beta1 and P III P which in these three investigated groups.</p><p><b>RESULTS</b>Drug treatment group and complex treatment group of patients improved the clinical symptoms and lung function Compared with Pretreatment, the FVC, FEV1.0, FEV1.0/FVC, MVV was obviously higher than those before treatment (P < 0.05). Complex treatment group than in the drug treatment group increased more significantly (P < 0.05). The level of TGF-beta1 and P III P was reduced after complex treatment (P < 0.05). Moreover,the level of TGF-beta1 and P III P in these patients are lower than in those patients treated with tetrandrine combined with whole lung lavage (P < 0.05).</p><p><b>CONCLUSION</b>Tetrandrine combined with whole-lung lavage could significantly retard the development of pneumoconiosis by lessening the TGF-beta1 and P III P in serum.</p>
Subject(s)
Adult , Humans , Male , Middle Aged , Benzylisoquinolines , Therapeutic Uses , Bronchoalveolar Lavage , Collagen Type III , Blood , Combined Modality Therapy , Pneumoconiosis , Blood , Therapeutics , Transforming Growth Factor beta1 , Blood , Treatment OutcomeABSTRACT
A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (x2 = 6.79, P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance (x2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Carrier Proteins , Genetics , Gene Frequency , Genotype , Hepatitis B , Genetics , Liver Cirrhosis , Genetics , Ornithine Decarboxylase Inhibitors , Polymorphism, Single NucleotideABSTRACT
<p><b>OBJECTIVE</b>To observe the curative effect of HanFangJiaSu on pneumoconiosis.</p><p><b>METHOD</b>71 patients with silicosis were divided into trial group and control group at random. The treating group (36 patients) was treated 90 days with HanFangJiaSu and The control group (35 patients) was treated 90 days with XiFeiNing. The silicosis with cough,chest complaint, dyspnoea and immune modulation were observed before treating and after treating. The effect was compared between the two groups.</p><p><b>RESULT</b>To compared with the group before treatment and the control group, the symptoms score of cough, chest complaint and dyspnoea in treated group was significantly decreased after treatment(P<0.05). The rate was decreased by 69.35% in treated group and 50.00% in controls, which showed the treatment in both groups was effective. The rate in treated group was significantly decreased more than in controls(P<0.05). There were 13 cases with respiratory tract infection and 2 cases with lung infection in treated group of which percentage were 36.11% and 5.55%, while 22 cases and 4 cases in control group of which percentage were 57.14% and 28.57%. There was a significant difference between the two groups (P<0.05). To compared with the group before treatment, the quantity of CD(4) in blood was obviously increased, while CD(8) was obviously decreased, which showed a significant increase of CD(4)/ CD(8), (P<0.05). To compared with control group, the quantity of CD(4) in treated group was obviously increased, while CD8 was obviously decreased, which also showed a significant increase of CD(4)/CD(8) (P<0.05). There was no significant difference with the concentration of immune globulin (IgG, IgA, IgM) between the groups before and after treatment.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , CD4-CD8 Ratio , Drugs, Chinese Herbal , Therapeutic Uses , Phytotherapy , Silicosis , Drug Therapy , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>The staging and treatment of bronchioloalveolar carcinoma (BAC) with pulmonary metastasis are still controversial. This study aimed at evaluating the current staging of BAC with ipsilateral intrapulmonary metastatic nodules and the therapeutic effectiveness of surgical resection.</p><p><b>METHODS</b>The clinicopathological data of 729 completely and surgically resected patients with non-small cell lung cancer (NSCLC) from December 1999 to December 2006 were retrospectively reviewed. Prognostic factors affecting the overall survival were analyzed by the Kaplan-Meier method and compared by the log rank test.</p><p><b>RESULTS</b>Among 67 NSCLC patients with ipsilateral intrapulmonary metastatic nodules, 54 had multiple nodules in the lobe with primary lesion (T4, PM1) and 13 had additional nodules in the other ipsilateral lobes (M1, PM2). This series consisted of 40 males and 27 females, with a median age of 60.0 years. Of those, 28 had the lesions containing pure or some bronchioloalveolar carcinoma component, while the other 39 had a NSCLC lesions containing non-bronchioloalveolar carcinoma components. The median overall survival time of this series was 24.0 months. Prognostic study demonstrated that bronchioloalveolar carcinoma histology and mediastinal lymph node metastasis had significant adverse impact on the overall survival. The median survival time of the patients with bronchioloalveolar carcinoma was 58.0 months versus 27.0 months in patients with other subtypes of NSCLC (P < 0.01). The median survival times were 39.0 months for the patients with N0 or N1 versus 14.0 months for patients with N2, with a significant difference between the two groups (P < 0.01). There was no significant difference in the survival time between the patients with PM1 (36 months) and those with PM2 (24 months) (P > 0.05).</p><p><b>CONCLUSION</b>Surgical resection is effective for NSCLC patients with ipsilateral intra-pulmonary metastasis, especially for those with bronchioloalveolar carcinoma components. Our results suggest that the current TNM classification system may be inappropriate for the NSCLC patients with ipsilateral intrapulmonary metastatic nodules, and may need a modification.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma, Bronchiolo-Alveolar , Pathology , General Surgery , Carcinoma, Non-Small-Cell Lung , Pathology , General Surgery , Follow-Up Studies , Lung Neoplasms , Pathology , General Surgery , Lymph Node Excision , Lymph Nodes , Pathology , Lymphatic Metastasis , Mediastinum , Neoplasm Staging , Pneumonectomy , Methods , Retrospective Studies , Survival RateABSTRACT
<p><b>OBJECTIVES</b>The staging and treatment of multi-focal non-small cell lung cancer (NSCLC) are controversial. This study evaluated the effectiveness of surgical treatment for the ipsilateral multi-focal NSCLC.</p><p><b>METHODS</b>Sixty-eight patients with multi-focal NSCLC underwent complete resection from December 1999 to December 2006. This series included 44 males and 24 females, with a mean age of 60.3 years old (range from 33 to 81 years old). Fifty-four patients had multiple nodules in primary lobe (T4) and 13 patients had additional nodules in non-primary lobe (M1), and a patient was proved to have synchronous primary NSCLC lesions. Surgical treatments included lobectomy in 53 cases, bilobectomy in 4 cases, pneumonectomy in 2 cases, and lobectomy combined with wedge resection in 9 cases.</p><p><b>RESULTS</b>The median overall survival time of this series was 30 months. Prognostic study demonstrated that mediastinal lymph node metastasis and bronchioloalveolar carcinoma histology had significant impact on overall survival. The median survival times were 39 months for patients with N0 and N1, and 14 months for patients with N2, respectively, and there was significant difference between the groups (P < 0.01). The difference in survival was significant between patients with bronchioloalveolar carcinoma components and other NSCLC histologic types (P < 0.01), and the median survival times were 46 months and 20 months, respectively.</p><p><b>CONCLUSION</b>Surgery could provide choice for multi-focal NSCLC patients (T4 and M1), especially for patients with bronchioloalveolar carcinoma components and without mediastinal lymph node metastasis.</p>