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.

Objective To evaluate the influence of hepatic ischemia-repeffusion injury (HIRI) induced by Pringle maneuver on the prognosis of hepatoceUular carcinoma (HCC) patients after hepatectomy. Methods The chnical data of 315 HCC patients who had been admitted to Southwest Hospital from January 2004 to December 2008 were retrospectively analyzed. The 194 patients who received Pringle maneuver during hepatectomy were in the HIRI group. The control group was composed of 121 patients without portal triad clamping. The pre- and peri-operative characteristics and the prognosis of the patients were analyzed by t test, chi-square test, Kaplan-Meier survival curve, Log-rank test and Cox regression model analysis. Results Patients in the HIRI group were significantly younger than those in control group (median age, 49 vs 59) (X2 =4. 12, P < 0.05). There were 108 patients (55.7%) with large HCC (diameter > 5 cm) in the HIRI group, while the number of patients with large HCC in the control group was 83 (68.6%), with statistical difference between the 2 groups (X2=4. 12, P <0.05). The serum levels of aspartate aminotransferase on postoperative day 3 and day 7 were 255 U/L and 112 U/L, which were significantly higher than 128 U/L and 35 U/L in the control group (X2 =4.57, 5.89, P <0.05). The level of total bilirubin on postoperative day 3 was 56 U/L in the HIRI group, which was significantly higher than 39 U/L in the control group (X2=4.79, P <0.05). The disease-free survival rate and cumulative survival rate in the HIRI group were significantly lower than those in the control group (X2 = 5.93, 8. 32, P < 0. 05). Perioperative blood loss, diameter of tumor, portal triad clamping and portal vein invasion were independent factors influencing the diseasefree survival rate. Conclusions HIRI induced by Pringle maneuver significantly decreases the disease-free survival rate and cumulative survival rate of HCC patients after hepatectomy.

Objective To explore the clinical value of virtual touch quantification technique(VTQ)and fibroscan technique for the diagnosis of hepatic fibrosis.Methods A total of 1 02 patients with chronic liver disease and 78 normal individuals were enrolled in the study.They were all examined with VTQ and fibroscan technique.Pathological results were used as standard criterion.Results The liver tissue riqidity was associated with pathological results.The coefficient of relativity was 0.43309(VTQ)and 0.35840(Fibroscan).ROC curve displayed that VTQ value of 1.4 m/s and fibroscan value of 7.75 kPa can be used to differential diagnose the lowgrade liver fibrosis and high-grade liver fibrosis.The probability of success was 100 0A(102/102)and 100%(78/78)by VTQ,but 88%(90/102)and 100%(78/78)by fibroscan technique.Conclusions VTQ and fibroscan technique are useful in the diagnosis of hepatic fibrosis.Compared with fibroscan technique,VTQ has more advantages in sensitivity practicability and convenience.

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

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

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