Adolescent ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Medicine, Chinese Traditional ; methods ; Ovarian Diseases ; physiopathology ; therapy ; Ovary ; physiopathology ; Phytotherapy ; Young Adult

The effects of magnolol (Mag) on hyperglycemia and hyperlipemia, hepatic oxidative stress and cytochrome P4502E1 (CYP2E1) activity of diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ) were studied. After oral administration of Mag (25, 50 and 100 mg x kg(-1) x d(-1)) for continuous 10 weeks, the blood glucose and lipids (TC, TG and LDL-C) levels, as well as the hepatic CYP2E1 activity and MDA content of diabetic rats, decreased significantly (P < 0.05 or P < 0.01), whereas the oral glucose tolerance and hepatic antioxidant enzymatic activities (CAT and GSH-Px) of diabetic rats, increased significantly (P < 0.05 or P < 0.01). The results indicated that Mag was effective against the hepatic oxidative damage, hyperglycemia and hyperlipemia of diabetic rats induced by HFD and STZ, and the inhibition of Mag on hepatic CYP2E1 activity could be an important mechanism of Mag against hepatic insulin resistance and oxidative damage.
Animals ; Biphenyl Compounds ; isolation & purification ; pharmacology ; Blood Glucose ; metabolism ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Cytochrome P-450 CYP2E1 ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; Diet, High-Fat ; Glucose Tolerance Test ; Hypoglycemic Agents ; isolation & purification ; pharmacology ; Lignans ; isolation & purification ; pharmacology ; Liver ; metabolism ; Magnolia ; chemistry ; Male ; Oxidative Stress ; drug effects ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Streptozocin ; Triglycerides ; blood

Bronchogenic Cyst ; Child ; Humans ; Male ; Neck ; pathology ; Young Adult

Animals ; Apoptosis ; drug effects ; Glutamic Acid ; pharmacology ; Oligonucleotides, Antisense ; pharmacology ; PC12 Cells ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Receptors, Thrombin ; antagonists & inhibitors ; genetics

To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.

Objective To investigate the effects of octacosanol on the behavioral changes and its potential mechanism in 6-hydroxydopamineinduced Parkinsonism rats. Methods 6-hydroxydopamine-induced Parkinsonism rats accepted octacosanol orally in the dosage of 17.5mg/kg (low dose), 35 mg/kg (medium dose) and 70 mg/kg (high dose) for 2 weeks, and then assessed with rotating test and narrow beam test. The apoptosis cells were counted with TUNEL assay, and the expression of nerve growth factor (NGF), precursor of nerve growth factor (proNGF), as well as their receptors were detected with Western blotting. Results The achievement of behavioral tests significantly improved after administration of octacosanol (P<0.05), with the decrease of the apoptotic cells, more expression of NGF and its receptors TrkA, and less expression of caspase-3, proNGF and its receptors p75NTR and sortilin, especially at the dosage of 70 mg/kg (P<0.05). Conclusion Octacosanol may protect the neurol impairment from 6-hydroxydopamine through NGF mediated pathway to decrease the apoptosis.

Objective To explore the effects of octacosanol on the behavioral impairments in rats with Parkinson's disease (PD) inducedby 6-hydroxydopamine (6-OHDA). Methods The SD rats were divided into the control group (n=15), the model group (n=15), the low dosegroup (n=12), the medium dose group (n=12) and the high dose group (n=12). 6-OHDA was stereotactically injected into the right striatumof the rats at 2 sites to produce PD models. The treatment groups received octacosanol with the dose of 17.5 mg/kg, 35 mg/kg or 70 mg/kgfor 2 weeks. They were tested with apomorphine-induced rotation test, the modified Morris Water Maze, and rotarod test. Results The contralateralrotation in 30 min and escape latency were less in the medium and high dose groups than in the model group (P<0.05); the latencyand total time in the rotarod test were significantly less in all the treatment groups than in the model group (P<0.01). Conclusion Octacosanolcan decrease the impaired behaviors of rats with PD induced by 6-OHDA.

Objective To investigate whether octacosanol would attenuate neurotoxicity in 1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Methods Behavioral tests, Nissl histochemistry and Western blot were used to investigate the effects of octacosanol in this mouse model of PD. Results Oral administration of octacosanol (100 mg/kg) significantly improved behavioral outcome in mice induced by MPTP and markedly ameliorated morphological appearances of neuronal cells in striatum. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. Conclusion The protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38 MAPK and JNK on the signal transduction in vivo.

Single cell "omics" technology enables the capture of genome, transcriptome, proteome and other omics information in a high-throughput and unbiased manner at single-cell resolution, allowing the characterization of the functional state of individual cells to reveal their heterogeneity and differential responses to drug treatment. This technology has wide application in pharmacological research, facilitating drug screening, efficacy evaluation, and mechanistic studies. We envision that, in the field of traditional Chinese medicine (TCM), single cell omics technology can be applied in the identification of active ingredients and drug targets, and elucidation of drug mechanism of action. In this article, we briefly introduce the single cell omics technology - particularly single cell transcriptome sequencing, and review its application in the field of modern drug research. Based on that, we propose the concept of "single cell pharmacology" and articulate how it can be applied to transform the pharmacological research of TCM and promote TCM modernization.

Objective To explore the bias between the real pressure and the measured values when handheld pressure gauge (HPG) was used to monitor intermittently the pressure in the intubation balloon,so as to provide some measures for the correct use of HPG.Methods In the first part of the study,HPG was used to measure the pressure with the balloon connected with a three-way tube with which to control the inflation and deflation in a laboratory to measure the pressure in the air bag.After gaining the deviation in this in vitro experiment,it was tested and verified in vivo in adult patients undergoing endotracheal intubation.Results After 132 times of measurements,it was found that measurement with a HPG might result in an inherent loss (3.928 ± 0.291) cmH2O (1 cmH2O=0.098 kPa,t =155.273,P =0.000) between inflation value [(30.000 ± 0.000) cmH2O] and measured value [(26.072 ± 0.291) cmH2O].In addition,after 214 times repeated measurements,the pressure loss during disconnection of the gauge was as high as (1.196 ± 0.954) cmH2O (t=18.348,P=0.000) between filled values [(30.000 ± 0.000) cmH2O] and measured values [(28.804 ± 0.954) cmH2O] and it was named as error loss.At last,the total error was verified by clinical test,and it was (5.270 ± 2.583) cmH2O (t=29.632,P=0.000) between pressure of filled value [(30.000 ± 0.000) cmH2O] and measured value [(24.730 ± 2.583) cmH2O].Conclusions When the balloon pressure was Monitored intermittently with HPG,the real value should be the measured value plus the error.In addition,subglottic aspiration should be done before the connection of the balloon to the gauge to prevent the secretions on the cuff falls into the deeper airway,and to maintain the cuff pressure at 30 cmH2O.