Animals ; Guanylate Cyclase ; metabolism ; Hypercapnia ; metabolism ; Hypoxia ; metabolism ; Lung ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Soluble Guanylyl Cyclase

Objectives: To investigate the effects of adhesion and proliferation of bone mesenchymal stem cells (BMSCs) in the surface of lactic acid/glycolic acid/asparagic acid-co-polyethylene glycol PLGA-[ASP-PEG] tri-block polymer scaffolds, try to find a new biomaterial to induce seed cells in vitro for bone tissue engineering. Methods: Modified PLGA with polyethylene glycol (PEG) and asparagic acid (ASP) that has many ligands, and synthesis PLGA-[ASP-PEG] polymer material. BMSCs were cultured in PLGA-[ASP-PEG] polymer material and PLGA used as control group. Through precipitation method, MTT assay and total cellular protein detection to test the adhersion and proliferation of BMSCs. Scanning electron microscope is used to observe cells appearance. Results: BMSCs on the surface of PLGA-[ASP-PEG] polymer scaffolds are adherention to the culture flask, the number of cells is much higher than PLGA’s. The precipitation method suggest that adhesion and proliferation of BMSCs on the surface of PLGA-[ASP-PEG] is much higher than the control group(P

Objective: To investigate the effects of the link between overweight/obesity and type 2 diabetes mellitus (T2DM) on leptin and visfatin levels. Methods: Males without T2DM and male patients with T2DM hospitalized in Lishui Municipal Central Hospital from January to June, 2017 were enrolled. Subjects' age and medical history of diseases were collected. The height and body weight were measured, and the body mass index (BMI) was estimated. The leptin and visfatin levels were determined, and compared between patients with and without T2DM, and between patients with and without overweight/obesity. The effect of the link between overweight/obesity and T2DM on leptin and visfatin levels was examined using a generalized linear regression model. Results: There were 66 patients with T2DM, with a mean age of (49.70±9.45) years and a mean diabetes duration of (4.99±4.46) years, and there were 64 patients without T2DM, with a mean age of (43.89±0.20) years. The leptin [ (3.17±0.36) vs. (3.03±0.30) ng/mL; t=2.387, P=0.018] and visfatin levels [ (29.14±3.16) vs. (21.81±3.32) ng/mL; t=12.900, P<0.001] were significantly greater in T2DM patients than in patients without T2DM. The leptin level was significantly greater in patients with overweight/obesity than in those without overweight/obesity [ (3.27±0.32) vs. (2.92±0.26) ng/mL; t=6.634, P<0.001], and the visfatin level was significantly lower in patients with overweight/obesity than in those without overweight/obesity [(24.38±5.14) vs. (26.71±4.36) ng/mL; t=2.780, P=0.006]. Generalized linear regression analysis showed interacting effects of overweight/obesity and T2DM on leptin (β=0.286, P=0.003) and visfatin levels (β=2.709, P=0.008). Conclusion The interaction between overweight/obesity and T2DM affects leptin and visfatin levels.

The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.

Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.

Animals ; Codonopsis ; chemistry ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Fatigue ; drug therapy ; Female ; Hypoxia ; drug therapy ; Male ; Mice ; Selenium ; pharmacology

Cell Membrane ; metabolism ; Gastrointestinal Stromal Tumors ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-kit ; analysis

BACKGROUNDAlthough the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines, the mechanisms by which cytokines induce anemia are poorly defined. This study focused on the mechanism research.

METHODSDifferent types of mice were infected perorally with Toxoplasma gondii strain ME49. At the indicated times, samples from each mouse were harvested, processed, and analyzed individually. Blood samples were analyzed using a Coulter Counter and red blood cell (RBC) survival was measured by biotinylation. Levels of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and inducible protein 10 (IP-10) mRNA in liver tissue were measured by real-time polymerase chain reaction.

RESULTST. gondii-infected mice exhibited anemia due to a decrease in both erythropoiesis and survival time of RBC in the circulation (P < 0.02). In addition, infection-stimulated anemia was associated with fecal occult, supporting previous literature that hemorrhage is a consequence of T. gondii infection in mice. Infection-induced anemia was abolished in interferon gamma (IFNγ) and IFNγ receptor deficient mice (P < 0.05) but was still evident in mice lacking TNF-α, iNOS, phagocyte NADPH oxidase or IP-10 (P < 0.02). Neither signal transducer and activator of transcription 1 (STAT1) deficient mice nor 129S6 controls exhibited decreased erythropoiesis, but rather suffered from an anemia resulting solely from increased loss of circulating RBC.

CONCLUSIONSInfection-stimulated decrease in erythropoiesis and losses of RBC have distinct mechanistic bases. These results show that during T. gondii infection, IFNγ is responsible for an anemia that results from both a decrease in erythropoiesis and a STAT1 independent loss of circulating RBC.

Anemia ; genetics ; metabolism ; Animals ; Erythrocytes ; pathology ; Interferon-gamma ; metabolism ; Male ; Mice ; Mice, Knockout ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Receptors, Interferon ; genetics ; metabolism ; STAT1 Transcription Factor ; genetics ; metabolism ; Toxoplasma ; pathogenicity ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Objective To compare the tumor sizes of primary lesions in pancreatic cancer based on CT scan and postoperative pathological analysis and measure the extent of filtration under a microscope,and to determine the CTV in radiotherapy target delineation.Methods A total of 19 patients with pancreatic cancer who were admitted to PLA General Hospital and Air Force General Hospital,PLA from 2013 to 2014 were analyzed.In 15 patients,the maximum diameters of tumor cross-section were measured based on the images of preoperative multi-slice spiral CT and postoperative gross samples,respectively.In 19 patients,the extent of tumor infiltration was measured on pathological sections under a microscope and the actual extent of infiltration was calculated.The paired t-test was applied to analyze the differences in the results of different measurement methods.Results In the 15 patients,the maximum tumor diameters measured with gross samples and CT scan were 33.6 mm and 30.1 mm,respectively (P=0.000),and the median and mean of the differences were 3.1 mm (1.2-8.0 mm) and 3.6±2.0 mm,respectively (95％ CI 1.2-6.0).In the 19 patients,the maximum actual infiltration distance and the maximum distance measured were 3.50 mm and 3.19 mm,respectively (P=0.000),and the median and mean of the differences were 0.31 mm (0.15-0.50 mm) and 0.30±0.09 mm,respectively.The maximum distance between the margin of primary lesions and the infiltrating lesions was 5.21 mm,with a median of 3.34 mm (2.19-5.21 mm) and a mean of 3.50± 0.88 mm (95％ CI 2.19-5.06).Conclusions Contrast-enhanced CT scan underestimates the actual size of primary lesions in pancreatic cancer,and an extension of 5 mm outside gross tumor volume (GTV) as CTV may not be sufficient.It is recommended to extend another 1-3 mm outside GTV as CTV.

With patients' general situation, medication use, occurrence time of adverse drug reaction/event (ADR/ADE), clinical manifestations and prognosis as reference items, a retrospective study was made for 315 cases with ADR/ADE induced by Gastrodin in Chongqing from January 2008 to June 2014, in order to analyze the characteristics of ADR/ADE and provide reference for rational clinical medication. The results showed that among the 315 cases with ADR/ADE, 143 cases (45.4%) were males and 172 cases (54.6%) were females, most of them (74.9%) were aged above 45; 60 cases (19.0%) with ADE were caused by off-label indications and 66 cases (21.0%) with ADE were caused by over dosage; ADR/ADE cases induced by intravenous drip mainly happened within 30 min (85.5%), ADR/ADE cases induced by oral administration mainly happened within 2 h (74.4%), and all of ADR/ ADE cases induced by intramuscular injection happened within 10 min. Totally 593 ADR/ADE cases were reported, which were mainly damages in gastrointestinal system, skin and its adnexa; And 61.9% of ADR/ADE cases were newly reported. It is suggested that medical workers shall learn about the regularity and characteristics of ADR/ADE induced by gastrodin, apply it in clinic with standards, pay close attention to changes of patients' situations and attach importance to the monitoring of ADR/ADE, so as to enhance the safety of medication.
Adolescent ; Adult ; Aged ; Benzyl Alcohols ; administration & dosage ; adverse effects ; Child ; Child, Preschool ; China ; epidemiology ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Gastrointestinal Tract ; drug effects ; Glucosides ; administration & dosage ; adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Skin ; drug effects ; Young Adult