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

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

OBJECTIVETo explore the cure effects of Jiangu Fufang on osteoporotic model induced by ovariectomy.

METHODRats were ovariectomized and administered drugs for 3 monthes. Bone mineral density and biomechanics properties, histomorphometric analysis and biochemical index such as calcium, phosphorus, alkaline phosphatase were detected.

RESULTJiangu Fufang could significantly increase bone density and biomechanics properties. The level of calcium, phosphorus and alkaline phosphatase were restored by Jiangu Fufang. Jiangu Fufang could significantly increase area of bone trabecula, thickness of cortical bone and bone trabecula.

CONCLUSIONJiangu Fufang could cure osteoporosis through increasing bone mineral density, improving bone biomechanics properties, and effecting bone metabolism.

Alkaline Phosphatase ; blood ; Animals ; Biomechanical Phenomena ; Bone Density ; drug effects ; Calcium ; blood ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Female ; Femur ; physiopathology ; Lumbar Vertebrae ; drug effects ; pathology ; physiopathology ; Osteoporosis ; blood ; drug therapy ; physiopathology ; Ovariectomy ; Phosphorus ; blood ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

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

SARS-CoV is a newly discovery pathogen causing severe acute respiratory problems.It has been established that the S protein in this pathogen plays an important rule in the adsorption and penetration of SARS-CoV into the host cell by interaction with the ACE2 receptor.To determinant which functional motif of the S protein was involved in the interaction with ACE2,seven truncated S proteins deleted from the N or C terminal were obtained by an E.coli expression system and purified by column chromatography to homogeneity.Each truncated S protein was fixed on to the well of an ELISA plate and an interaction was initiated with the ACE2 protein.The adsorption were quantified by ELISA,and the results indicated that amino acids from 388 to 496 of the S protein was responsible for the interaction with the ACE2 receptor,and the interaction could be completely disrupted by an antibody specific to these amino acids.Deletions adjacent to this domain did not appear to have a significant impact on the interaction with ACE2,suggesting that the S protein of SARS-CoV could be developed as a vaccine to prevent the spread of SARS-CoV.

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