In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
Rats ; Animals ; Periploca ; Cysteine ; Cytidine Diphosphate Choline ; Network Pharmacology ; Phosphorylcholine ; Metabolomics ; Arthritis, Rheumatoid/drug therapy* ; Biomarkers ; Glycerophospholipids ; Methionine ; Purines ; Chromatography, High Pressure Liquid

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 μg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10^-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.
Anti-Bacterial Agents/pharmacology* ; Bacterial Proteins/metabolism* ; Biofilms ; Molecular Docking Simulation ; Phosphorylcholine/analogs & derivatives* ; Pseudomonas aeruginosa/metabolism* ; Quorum Sensing

Accumulating data have revealed that abnormal activity of the mTOR (mammalian target of rapamycin) pathway plays an important role in epileptogenesis triggered by various factors. We previously reported that pretreatment with perifosine, an inhibitor of Akt (also called protein kinase B), abolishes the rapamycin-induced paradoxical increase of S6 phosphorylation in a rat model induced by kainic acid (KA). Since Akt is an upstream target in the mTOR signaling pathway, we set out to determine whether perifosine has a preventive effect on epileptogenesis. Here, we explored the effect of perifosine on the model of temporal epilepsy induced by KA in rats and found that pretreatment with perifosine had no effect on the severity or duration of the KA-induced status epilepticus. However, perifosine almost completely inhibited the activation of p-Akt and p-S6 both acutely and chronically following the KA-induced status epilepticus. Perifosine pretreatment suppressed the KA-induced neuronal death and mossy fiber sprouting. The frequency of spontaneous seizures was markedly decreased in rats pretreated with perifosine. Accordingly, rats pretreated with perifosine showed mild impairment in cognitive functions. Collectively, this study provides novel evidence in a KA seizure model that perifosine may be a potential drug for use in anti-epileptogenic therapy.
Animals ; Anticonvulsants ; pharmacology ; Brain ; drug effects ; pathology ; Convulsants ; toxicity ; Disease Models, Animal ; Epilepsy, Temporal Lobe ; chemically induced ; pathology ; Kainic Acid ; toxicity ; Male ; Neurons ; drug effects ; pathology ; Phosphorylcholine ; analogs & derivatives ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; chemically induced ; pathology

Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate (DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent (MPC) and antibacterial agent (DMAHDM) were added to a Scotchbond multi-purpose (SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days (d). At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control (P < 0.05). The SBMP + MPC + DMAHDM group had protein adhesion that was only 1/20 of that of the SBMP control (P < 0.05). Incorporation of MPC and DMAHDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d (P > 0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.
Anti-Infective Agents ; chemistry ; pharmacology ; Biofilms ; drug effects ; Dental Bonding ; Dentin-Bonding Agents ; chemistry ; pharmacology ; Materials Testing ; Methacrylates ; chemistry ; pharmacology ; Phosphorylcholine ; analogs & derivatives ; chemistry ; pharmacology ; Resin Cements ; Shear Strength ; Surface Properties ; Water

OBJECTIVETo evaluate the effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) and nanoparticles of amorphous calcium phosphate (NACP) on the protein-repellent property of dental adhesive.

METHODSMPC and NACP were incorporated into SBMP as the test group. Scotchbond Multi-Purpose (SBMP) was used as control group. Human dentin shear bond strengths were measured. Protein adsorption onto samples was determined by micro bicinchoninic acid (BCA) method. A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm viability.

RESULTSThe dentin bond strength of modified group was (28.7±2.2) MPa, which was not significantly different from that of the SBMP control group. The amount of protein adsorption in the modified group and the SBMP control group were (0.21±0.02) µg/cm(2) and (4.17±0.45) µg/cm(2) respectively. Lactic acid production of biofilms in modified group and SBMP control were (7.71 ± 1.01) mmol/L and (19.18 ± 2.34) mmol/L repectively.

CONCLUSIONSMPC-NACP based dental adhesive greatly reduce the protein adsorption and bacterial adhesion, without compromising dentin shear bond strength. This novel bonding agent may have wide application.

Adsorption ; Biofilms ; drug effects ; growth & development ; Calcium Phosphates ; pharmacology ; Dental Cements ; pharmacology ; Dental Plaque ; Dentin ; chemistry ; Humans ; Lactic Acid ; biosynthesis ; Methacrylates ; pharmacology ; Nanoparticles ; Phosphorylcholine ; analogs & derivatives ; pharmacology ; Resin Cements ; pharmacology ; Saliva ; Tensile Strength

OBJECTIVEThis paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs).

DATA SOURCESAll articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect.

STUDY SELECTIONThe articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded.

RESULTSTechnology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments.

CONCLUSIONThe surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.

Animals ; Heparin ; chemistry ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lenses, Intraocular ; Methacrylates ; chemistry ; Ozone ; chemistry ; Phosphorylcholine ; analogs & derivatives ; chemistry ; Ultraviolet Rays

Secondary caries due to biofilm acids is a primary cause of dental composite restoration failure. To date, there have been no reports of dental composites that can repel protein adsorption and inhibit bacteria attachment. The objectives of this study were to develop a protein-repellent dental composite by incorporating 2-methacryloyloxyethyl phosphorylcholine (MPC) and to investigate for the first time the effects of MPC mass fraction on protein adsorption, bacteria attachment, biofilm growth, and mechanical properties. Composites were synthesized with 0 (control), 0.75%, 1.5%, 2.25%, 3%, 4.5% and 6% of MPC by mass. A commercial composite was also tested as a control. Mechanical properties were measured in three-point flexure. Protein adsorption onto the composite was determined by the microbicinchoninic acid method. A human saliva microcosm biofilm model was used. Early attachment at 4 h, biofilm at 2 days, live/dead staining and colony-forming units (CFUs) of biofilms grown on the composites were investigated. Composites with MPC of up to 3% had mechanical properties similar to those without MPC and those of the commercial control, whereas 4.5% and 6% MPC decreased the mechanical properties (P<0.05). Increasing MPC from 0 to 3% reduced the protein adsorption on composites (P<0.05). The composite with 3% MPC had protein adsorption that was 1/12 that of the control (P<0.05). Oral bacteria early attachment and biofilm growth were also greatly reduced on the composite with 3% MPC, compared to the control (P<0.05). In conclusion, incorporation of MPC into composites at 3% greatly reduced protein adsorption, bacteria attachment and biofilm CFUs, without compromising mechanical properties. Protein-repellent composites could help to repel bacteria attachment and plaque build-up to reduce secondary caries. The protein-repellent method might be applicable to other dental materials.
Adsorption ; Biofilms ; Colony Count, Microbial ; Composite Resins ; chemistry ; Dental Plaque ; microbiology ; Methacrylates ; analysis ; Phosphorylcholine ; analogs & derivatives ; analysis ; Proteins ; chemistry

PURPOSE: A significant proportion of patients with cough variant asthma (CVA) eventually develops asthma. The aim of this study was to investigate the relationship between bronchial hyperresponsiveness (BHR) and development of asthma in preschool children with CVA. METHODS: We reviewed the medical records of children aged 5 to 7 years who presented with chronic cough and had regular check-up by the school age. All children had methacholine bronchial challenge test (MBCT) at preschool age with a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. Positive BHR was defined as end-point concentration (EPC)< or =8 mg/mL. MBCT was performed at the school age with spirometric method. Positive BHR was defined as PC20< or =8 mg/mL. We collected information on the development of wheezing or dyspnoea from the medical records. RESULTS: Thirty-six children with CVA were analyzed. During follow-up (2.1+/-0.9 years), 9/36 children developed wheezing or dyspnoea (group A), and 27/36 children did not (group B). EPC (geometric mean, 95% confidence interval) was significantly lower in group A than group B (1.59 mg/mL, 0.93 to 2.70 mg/mL vs. 3.43 mg/mL, 2.34 to 5.03 mg/mL; P=0.02, respectively). The prevalence of positive BHR at school age was significantly higher in group A than group B (77.8% vs. 22.2%, P<0.01). CONCLUSION: These results suggest that the increase and the persistence of BHR may have an important role in the development of asthma during the course of CVA in preschool children.
Aged ; Asthma ; Auscultation ; Bronchial Provocation Tests ; Child ; Child, Preschool ; Cough ; Follow-Up Studies ; Humans ; Medical Records ; Methacholine Chloride ; Oxygen ; Phosphorylcholine ; Prevalence ; Respiratory Sounds

BACKGROUND AND OBJECTIVES: Circulating endothelial progenitor cells (EPCs) play a key role in the maintenance of endothelial homeostasis and promote vascular repair. A reduced number of EPCs and the functional activity have been associated with several cardiovascular risk factors. However, the relationship between the number of EPCs and circadian rhythm of the blood pressure (BP) remains unclear. The purpose of the present study was to evaluate the relationship between the circadian rhythm of the BP and EPCs in patients with essential hypertension. SUBJECTS AND METHODS: A total of 45 patients with essential hypertension who were newly identified by outpatient BP measurements, underwent 24-hour ambulatory BP monitoring. Among the 45 patients with essential hypertension, 20 were classified as dippers (12 men and 8 women; mean age 48+/-14 years) and 25 as non-dippers (14 men and 11 women; mean age 52+/-18 years). The EPC count was isolated from the peripheral bloodstream and quantified by flow cytometry. RESULTS: The baseline clinical characteristics were similar between the dipper and non-dipper hypertensive patients. The circulating EPCs were statistically reduced in the non-dipper patients as compared to the dippers (104+/-60 vs. 66+/-47 EPCs per 106 mononuclear cells, p=0.027). The circulating EPC level correlated positively with the circadian changes in the systolic and diastolic BP (r=0.435, p=0.003, and r=0.310, p=0.038, respectively). CONCLUSION: The present study demonstrated that the EPC count was reduced in the peripheral bloodstream in non-dipper hypertensive patients.
Blood Pressure ; Circadian Rhythm ; Homeostasis ; Humans ; Hypertension ; Male ; Outpatients ; Phosphorylcholine ; Risk Factors ; Stem Cells

Probabilistic ecological risk assessment (PERA) for deriving ecological protective concentration (EPC) was previously suggested in USA, Australia, New Zealand, Canada, and Netherland. This study suggested the EPC of cadmium (Cd) based on the PERA to be suitable to Korean aquatic ecosystem. First, we collected reliable ecotoxicity data from reliable data without restriction and reliable data with restrictions. Next, we sorted the ecotoxicity data based on the site-specific locations, exposure duration, and water hardness. To correct toxicity by the water hardness, EU's hardness corrected algorithm was used with slope factor 0.89 and a benchmark of water hardness 100. EPC was calculated according to statistical extrapolation method (SEM), statistical extrapolation methodAcute to chronic ratio (SEMACR), and assessment factor method (AFM). As a result, aquatic toxicity data of Cd were collected from 43 acute toxicity data (4 Actinopterygill, 29 Branchiopoda, 1 Polychaeta, 2 Bryozoa, 6 Chlorophyceae, 1 Chanophyceae) and 40 chronic toxicity data (2 Actinopterygill, 23 Branchiopoda, 9 Chlorophyceae, 6 Macrophytes). Because toxicity data of Cd belongs to 4 classes in taxonomical classification, acute and chronic EPC (11.07 microg/l and 0.034 microg/l, respectively) was calculated according to SEM technique. These values were included in the range of international EPCs. This study would be useful to establish the ecological standard for the protection of aquatic ecosystem in Korea.
Australia ; Bryozoa ; Cadmium ; Canada ; Ecosystem ; Hardness ; Korea ; New Zealand ; Phosphorylcholine ; Polychaeta ; Risk Assessment ; Water