Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.
Dipeptidyl-Peptidase IV Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Drug Discovery ; methods ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; Linagliptin ; chemical synthesis ; chemistry ; Molecular Structure ; Piperidines ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Uracil ; analogs & derivatives ; chemical synthesis ; chemistry

Objective To assess the safety among acute ischemic stroke patients with asymptomatic intracranial aneurysm after the administration of intravenous thrombolysis.Methods We searched database including Wanfang,CNKI,VIP,Pubmed,EMBASE,EBSCO HOST and Metstr data for all the cohort studies on the use of thrombolysis for acute ischemic patients with asymptomatic intracranial aneurysm,and ascended the correlated references listed on the articles.Meta-analysis was conducted based on the methods recommended by the Cochrane collaboration.The outcomes of the meta-analysis were intracerebral hemorrhage (ICH),symptomatic intracerebral hemorrhage (sICH),subarachnoid hemorrhage (SAH).Results Four cohort studies included 707 patients,of whom 48 patients had asymptomatic cerebral aneurysms.The risk ratio prevalence of ICH among those patients did not differ statistically with those without aneurysms (RR =1.17,95％ CI 0.69-1.99,P =0.56).No statistical differences were found in both odds ratio prevalence of sICH (OR =1.70,95％ CI 0.44-6.59,P =0.45) and SAH (OR =1.13,95％ CI 0.20-6.27,P =0.89) between the patients with asymptomatic cerebral aneurysms and those without.Conclusion Current evidence did not indicate that the risk of hemorrhage increased in acute ischemic stroke patients with asymptomatic intracranial aneurysm after the administration of intravenous thrombolysis.

Adult ; Aged ; Bone Screws ; Calcaneus ; injuries ; surgery ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged

OBJECTIVETo study the effects of Si-Wu-Tang on serum protein of blood deficient mice b y proteomicstechnique and study the enriching and regulating blood mechanism of Si-Wu-Tang on mocular level.

METHODThe blood deficient mice was induced by using a single dose of 3.5 Gy radiation from a 60Cogamma source, and high resolution two-dimensional polyacryamide gel electrophoresis (2-DE), computer-assisted image analysis, and mass spectrometry were used to detect regulated protein by Si-Wu-Tang.

RESULT12 lower and 4 higher protein in sera could be recovered by Si-Wu-Tang, 4 protein might be DNA-dependent protein kinase catalytic subunit, Dystrophin, KIF13A, dystonin. They play a part in DNA double-stranded break repair, recombination and modulation of transcription, transportation of mannose-6-phosphate receptor, etc.

CONCLUSIONSi-Wu-Tang can regulate serum protein in blood deficient mice, resulting in improving hematopoiesis and lessening irradiated injury.

Animals ; Autoantigens ; blood ; Carrier Proteins ; Cytoskeletal Proteins ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Dystonin ; Dystrophin ; blood ; Female ; Kinesin ; blood ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; Non-Fibrillar Collagens ; blood ; Plants, Medicinal ; chemistry ; Radiation Injuries, Experimental ; blood ; Radiation-Protective Agents ; pharmacology ; Whole-Body Irradiation

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Caco-2 Cells ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Up-Regulation ; drug effects

OBJECTIVETo investigate the characteristics of the spontaneous isolated superior mesenteric artery dissection (SISMAD) on computed tomography angiography (CTA).

METHODSTwenty-five patients with unexplained acute abdominal pain received CTA.

RESULTSFour cases with the SISMAD were found and all were male with a mean age of (45.3±6.7) years. Two patients had hypertension history. CT showed enlarged diameter of the superior mesenteric artery with dissection in 4 cases, intimal flap and visible false lumen in 2 cases, ulcer-like laceration in 1 case, and intramural hematoma in 1 case. The proximal lacerations or entries were all at the proximal segment of the superior mesenteric artery. CTA classifications were type Ia (n=2), IIb (n=1), and III (n=1). Two patients underwent repeated CTA when discharged, and progressive changes were discovered.

CONCLUSIONCTA can clearly show the characteristics of the superior mesenteric artery dissection, confirm the diagnosis, and provide an important basis for the classification and follow-up observation.

Adult ; Aged ; Aged, 80 and over ; Aneurysm, Dissecting ; diagnostic imaging ; Angiography ; methods ; Female ; Humans ; Male ; Mesenteric Artery, Superior ; diagnostic imaging ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo study the effects of Siwu decoction on protein expression of blood deficiency mice induced by cyclophosphamide (CIX) and discuss the possible molecular mechanism on blood enriching function of Siwu decoction.

METHODBlood deficiency mice were established by injecting ip with 250 mg x kg(-1) CTX. Proteomic technologies were applied to identify the different protein.

RESULTSiwu decoction could restore the changes of 12 up-regulated and 3 down-regulated proteins in bone marrow of blood deficiency mice induced by cyclosphosphamide.

CONCLUSIONSiwu decoction could effect expression of proteins which functions including apoptosis, proliferation and differentiation of the haematopoietic stem/progenitor cell. The regulation in the molecular level might be the mechanism of stimulating hematopoiesis in bone marrow fo siwu decocetion.

Actin Depolymerizing Factors ; metabolism ; Anemia ; chemically induced ; metabolism ; pathology ; Animals ; Annexin A1 ; metabolism ; Apoptosis ; drug effects ; Carbonic Anhydrases ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cyclophosphamide ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fatigue ; chemically induced ; metabolism ; pathology ; Female ; Hematopoietic Stem Cells ; metabolism ; pathology ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Peroxidases ; metabolism ; Peroxiredoxins ; Plants, Medicinal ; chemistry ; Proteome ; metabolism ; Proteomics ; methods

OBJECTIVETo research the effects of fufangdenshen tablets on atherosclerotic plasma protein using proteomic technique and further explore its potential molecular mechanism to cure atherosclerosis.

METHODThe plasma of normal, atherosclerosis and cured group were collected, and the albumin in plasma was removed. Proteomic protocol involved of 2-DE, image analysis and spectrometry detection was used to detect regulated plasma protein by fufangdenshen tablets.

RESULT3 decreased expressed and 6 higher protein in atherosclerotic plasma could be recovered by fufangdenshen tablets. The levels of fibrinogen, Granzyme C and immunoglobulin were decreased by fufangdenshen tablets.

CONCLUSIONThe levels of fibrinogen, Granzyme C in atherosclerotic plasma could be decreased by fufangdenshen tablets. The effects of fufangdenshen tablets on atherosclerosis included that: inhibition of adhesion of monocyte, inhibition of proliferation and migration of VSMC, and weakening of inflammation.

Aged ; Coronary Artery Disease ; blood ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Fibrinogen ; metabolism ; Granzymes ; blood ; Humans ; Immunoglobulins ; blood ; Middle Aged ; Plants, Medicinal ; chemistry ; Proteomics ; Salvia miltiorrhiza ; chemistry ; Tablets

Objective: To investigate the efficacy and safety of naftopidil on patients with mild-to-moderate essential hypertension. Methods: A prospective, open study was performed in patients with hyp ertension. Forty patients were administered naftopidil for 8 weeks. Results:BP decreased significantly 2 weeks after administration an d reached to its trough at week 4. The magnitudes were 2.28 kPa (17.1 mmHg) and 1.43 kPa (10.7 mmHg) for SBP and DBP, respectively. The effect lasted to the end of experiment. HR had no change.The total effective rate was 82.05%.There was n o significant change in liver and renal function and electrocardiograph. Conclusion: Naftopidil has a stable hypotensive effect and the complia nce is good.

Chemogenomics/chemical genomics has been widely used in novel drug research and discovery. Firstly, the concept of chemogenomics was introduced briefly. Secondly, we reviewed the progress of novel drug research and discovery based on forward chemogenomics, reverse chemogenomics and predictive chemogenomics. Finally, we showed progress of the research that chemogenomics has been used to novel drug research and discovery in pharmaceuticals companies.
Animals ; Drug Delivery Systems ; Drug Discovery ; methods ; Drug Industry ; trends ; Genomics ; methods ; Humans ; Pharmacogenetics ; methods