Latest ArticlesConjugated linoleic acid (CLA) is a nutrient substance that exists in humans and animals. It has anti-tumor, anti-atherosclerosis, and immune-regulating functions, but its oral bioavailability is low. Conjugated linoleic acid dry powder inhalers (CDPIs) were prepared and intratracheally administered to the rats that suffered from primary lung cancer. Conjugated linoleic acid nanoemulsions were prepared first and CDPIs were with 10% mannitol after lyophilization. CDPIs are loose white powders with the aerodynamic median diameter (Da) of 3.10 μm, which were suitable for pulmonary delivery. Rats lung cancer models were established after 45 days by instilling 3-methylcholanthrene (MCA) and N, N-dimethylnitrosamine (DEN) into the rats lung once. The animal experiments were approved by the Ethics Committee of Academy of Military Medical Sciences and conducted in accordance with the relevant guidelines and regulations. The CDPIs, gefitinib suspension and blank DPIs were sprayed into the lungs of rats with lung cancer through the trachea. Compared with the model group, both the gefitinib suspension group and the CDPIs group showed significantly fewer tumor nodules and inflammatory cells, and the CDPIs group was better than the gefitinib suspension group. The inhibition efficiency of CDPIs on CD31 and NF-κB p65 was better than that of the gefitinib suspension group. The vascular endothelial growth factor (VEGF) level in the CDPIs group was significantly reduced, which was equivalent to that of the gefitinib suspension group. The apoptosis in the CDPIs group by Tunel tests showed a significant increase, which was significantly better than the gefitinib suspension group. Therefore, CDPIs had excellent pharmacological activity on lung cancer, which provided a model for the efficient delivery of oil therapeutic agents.
Growth differentiation factor 15 (GDF15) is an endocrine hormone that belongs to the transforming growth factor β (TGFβ) superfamily, which plays a role by binding to the glial cell line derived neurotrophic factor (GDNF)-family receptor α-like (GFRAL)-rearranged during transfection (RET) heterodimer receptor. A number of studies have confirmed that GDF15, as a biomarker for obesity, diabetes, tumors, non-alcoholic fatty liver disease, ischemic diseases, and so on, has become a new target for new drug discovery. At present, pharmaceutical companies around the world are carrying out drug discovery with GDF15 as a new therapeutic target involving many therapeutic areas such as anti-obesity, anti-tumor, and treatment of anorexia syndrome. Comprehensive analysis of the advantages and disadvantages of the GDF15 target, discussion, and objective evaluation of research and development of new drugs based on GDF15 will provide a scientific basis for the discovery of innovative drugs that could relieve the human suffering from illness.
As one of the most critical post-translational modifications, glycosylation of therapeutic proteins has a profound impact on their safety, efficacy and consistent. However, glycosylation is not a template-driven process, therefore variability in the glycosylation pattern of a protein can arise. This makes challenges of glycan analysis and control. Here, we review the overall control strategy, basic requirements for standardized protocols and the novel technologies of glycosylation analysis to accelerate the development of therapeutic glycoproteins.
In recent years, the research on myocardial ischemia disease is increasingly in-depth, and there are more and more drugs related to the anti-myocardial ischemia, among which natural medicines play an important role. In order to deal with myocardial ischemia diseases caused by a variety of pathogenic causes, the research on natural medicines is more and more deep. At present, natural medicines containing saponins, flavonoids, alkaloids and other compounds are the research objects. At the same time, great progress has been made in the research on the clinical application of natural drugs against myocardial ischemia. This article reviews the research progress of natural medicines against myocardial ischemia at home and abroad in the past ten years.
The activity and expression of drug metabolizing enzymes and transporters changes significantly under high altitude hypoxia. The gut microbiota is an important factor affecting the metabolism of drugs through direct and indirect actions, changing the bioavailability, biological activity or toxicity of drugs and affecting the efficacy and safety of drugs. High altitude hypoxia significantly changes the structure and diversity of the gut microbiota, which may play a role in drug metabolism. This article reviews the effects of high-altitude hypoxia on the gut microbiota and the effects these changes on drug metabolism.
To explore the preventive effects and potential mechanism of mulberry leaf water extract (MLWE) on type 2 diabetes mellitus (T2DM), this study observed the influence of MLWE on the metabolism of arachidonic acid (AA). T2DM mice were induced by high fat and high sucrose (HFHS) diet and intra-peritoneal injection of streptozotocin. The mice were randomly divided into a normal control group treated with drug-free solution (NC group), a normal control group treated with MLWE (NCML group), a diabetes mellitus (DM) group treated with drug-free solution (HFHS group), and a DM group treated with MLWE (HSML group); mice were maintained on this protocol for 10 weeks. Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Xuzhou Medical University. Mice livers and plasma were collected at the end of experiment. Fasting blood glucose (FBG) and fasting blood insulin (FBI) were detected by kits. The mRNA and protein expression levels of relative metabolic enzymes related to AA in mice livers were respectively detected by quantitative real time PCR (qPCR) and Western blot. The contents of AA and its relative metabolites in mice plasma were determined by liquid phase chromatography coupled with tandem mass spectrometry. The results showed that there was no significant variation for the relative expression of metabolic enzymes, contents of FBG, FBI, AA, and its relative metabolites between NCML group and NC group. Compared with NC group, the relative expression of fatty acid synthase (Fasn), phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and lipoxygenase-5 (LOX-5), and the levels of FBG, FBI, AA, and its relative metabolites in DM group were obviously increased, while that of carnitine palmitoyltransferase 1A (CPT1A) and cytochrome P450 family 4A (CYP4A) were significantly decreased. After intervention with MLWE, those changes could be improved, indicating that MLWE could prevent T2DM by acting on AA metabolism.
An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of seven components (chlorogenic acid, rutin, narirutin, hesperidin, sinensetin, nobiletin, tangeretin) in Citri Exocarpium Rubrum. The separation was performed over 12.0 min on a Shim-pack GIST C18 column (100 mm×2.1 mm, 2.0 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.4 mL·min-1; the column temperature was 30℃ and the injection volume was 1 μL. Detection was performed on a QTRAP 4500 mass spectrometer equipped with electrospray ionization. Positive and negative electrospray ionization was performed in multiple reaction monitoring mode. All of the analytes showed good linearity (r ≥ 0.997 3) in the tested ranges, with good precision, repeatability and stability for all analytes. The average recoveries were in the range of 99.32%-107.75% with relative standard deviations RSD ≤ 3.94%. The established method is accurate, stable and reproducible, and can provide a research method for the quality control of Citri Exocarpium Rubrum.
Five compounds were isolated from an ethanol extract of Artemisia deversa Diels by solvent extraction, Diaion HP-20, CHP20/P120 MCI, Sephadex LH-20, silica gel and preparative high performance liquid chromatography. Their structures were elucidated by MS, NMR and X-ray as artemideversal (1), 7-hydroxy-6-methoxycoumarin (2), 6, 7-dimethoxycoumarin (3), caffeic acid (4) and 4', 5, 7-trihydroxy flavone (5). Compound 1 is a new eudesmane-type sesquiterpene. In vitro cytotoxic activities of the five compounds were explored by MTT testing with HepG2, A549, HeLa and MRC-5 cell lines. Results show that compounds 1 and 5 significantly inhibited cellular proliferation. The IC50 of compound 1 in A549 and HepG2 cells was 8.36 and 16.51 μmol·L-1; the IC50 of compound 5 in A549 and HepG2 cells was 17.06 and 7.95 μmol·L-1.
Twenty-five quinolizidine alkaloids (including matrine-type 1-14, sparteine-type 15-17, cytisine-type 18-23, other types 24 and 25) were isolated from the roots and rhizomes of Sophora tonkinensis by various chromatographic methods. Their structures were elucidated by physicochemical properties, NMR and MS spectral data. Among them, 12-(1-acetoxyethyl)-cytisine (23) is a new alkaloid derivative, and compounds 13, 16, 17, 24 were isolated from the roots and rhizomes of S. tonkinensis for the first time. Compounds 1, 6, 19 and 20 showed potent inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages, with IC50 values of 39.86 ±0.65, 23.66 ±0.37, 34.56 ±0.45, 47.68 ±0.58 μmol·L-1, respectively.
We provide a new preclinical pharmacodynamic evaluation method of cerebral thrombolytics using beagle dogs with acute thrombotic cerebrovascular occlusion. An intracranial large vessel occlusion animal model was generated by pushing an autologous thrombus to the left carotid artery under X-ray angiography. The experiments were approved by the Animal Care and Welfare Committee Institute of Materia Medica, China Academy of Medical Sciences (CAMS), Peking Union Medical College. According to the degrees of cerebral blood flow reperfusion, the new method has 0, Ⅰ, Ⅱ (Ⅱa and Ⅱb), Ⅲ levels. Respectively, 0 level represents no blood flow through the area of vascular occlusion; Ⅰ level has low perfusion; Ⅱa level is less than half the infusion; Ⅱb level is more than half perfusion; Ⅲ level is completely recanalization perfusion. Alteplase was used as a positive drug to verify the accuracy of the method. Our results suggest that 100% of dogs reached the level of grade I and below in the model group, while 83% reached the level of grade IIa and above in the alteplase group. Results of a rank sum test showed that alteplase significantly improved the reperfusion of occluded cerebral vessels. We propose a method to evaluate the efficacy of thrombolytic drugs on dogs with middle cerebral artery occlusion.
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