N-Benzyl matrinol was obtained by hydrolysis, benzylation and reduction reaction from matrine. A series of hybrids (8a-8n) from (phenylsulfonyl)furoxan and N-benzyl matrinol were synthesized and biologically evaluated as anti-hepatocellular carcinoma agents. All target compounds were evaluated for anti-proliferative activity against human hepatocellular Bel-7402, SMMC-7721, Bel-7404, and HepG2 cells in vitro by MTT method. The results indicated that all of these compounds had potent anti-proliferative activity which were more potent than their parent compound and 5-FU, especially 8a-8h and 8j showed the strongest anti-HCC HepG2 cell activity with IC50 values of 0.12-0.93 μmol x L(-1).
Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; Fluorouracil ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Oxadiazoles ; pharmacology

The marine biological source of mineral drugs recorded in Chinese Pharmacopoeia (2010 version) mainly including pearl, nacre, clam shell, common oyster shell, ark shell, cuttle bone, and sea-ear shell are widely used in clinical. Calcium carbonate and a small amount of protein are the main components in this type of drugs. In this paper, a systematical and comparable study were carried out by determination of calcium carbonate by EDTA titration method, the crystal of calcium carbonate by X-Ray powder diffraction and the total amino acids (TAAs) of the hydrolyzed samples by ultraviolet spectrophotometry method. As a result, the crystal structure is calcite for common oyster shell, mixture of calcite and aragonite for nacre and sea-ear shell, aragonite for the other drugs. The content of calcium carbonate ranged from 86% to 96%. Cuttle bone has the highest amount of TAAs among the seven drugs which reached 1.7% while clam shell has the lowest content of 0.16% on average. In conclusion, an effective method was developed for the quality control of marine mineral drugs by comprehensive analysis of calcium carbonate and TAAs in the seven marine mineral drugs.
Amino Acids ; analysis ; chemistry ; Animal Shells ; chemistry ; Animals ; Calcium Carbonate ; analysis ; chemistry ; Crystallization ; Edetic Acid ; chemistry ; Mollusca ; chemistry ; classification ; Pharmaceutical Preparations ; analysis ; chemistry ; standards ; Quality Control ; Reproducibility of Results ; Seawater ; Species Specificity ; Spectrophotometry, Ultraviolet ; X-Ray Diffraction

OBJECTIVETo observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.

METHODSTotally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.

RESULTS(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).

CONCLUSIONSThe ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.

Animals ; Colforsin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; physiopathology ; Heart Failure, Diastolic ; drug therapy ; Isoproterenol ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Wistar

G,the noval insertion mutation of c.2298_2299insC is identified in Chinese patients.

BACKGROUND:The research and application of platelet-rich plasma in tissue regeneration and restoration have always been an issue of concern in the medicine and bioengineering fields.OBJECTIVE:To analyze the effects of platelet-rich plasma in combination with tendon stem cells on histomorphology change and matrix metalloproteinase 1 expression of the tendon tissues in a rabbit model of Achilles tendinopathy.METHODS:Forty New Zealand white rabbits were randomly divided into model group (n=32) and blank control group (n=8).In the model group,the animals were injected about 2 cm distant to the attachment point of the left calcaneus with prostaglandin E2 (once a week,for totally 4 weeks) to make the animal model of tendinopathy.The rabbits in the blank control group were injected the equal amount of normal saline.After 4 weeks,model rabbits were randomly divided into four subgroups:combination group,tendon stem cell group,platelet-rich plasma group and model control group,with eight rabbits in each group.Platelet-rich plasma and tendon stem cells,alone or in combination,and normal saline were injected into the corresponding group,twice with an interval of 3 weeks.At 6 weeks after injection,the tendon tissue was collected and stained for histological examination and detection of matrix metalloproteinasa 1 expression.RESULTS AND CONCLUSION:(1) Hematoxylin-eosin staining:the tendon fibers in the combinationgroup were intact and arranged orderly;in the tendon stem cell group,the tendon fibers were almost arranged orderly despite some fractured fibers;in the platelet-rich plasma group,fiber breakage and loose fiber structure were observed;in the model control group,there were no intact tendon fibers,with the presence of inflammatory cell filtration.(2) Masson staining:The tendon fibers in the combination group had slight wave-shaped changes but the fibers were not cut off;in the tendon stem cell group,the tendon fibers were slightly in disorder,but with the intact structure,and obvious inflammatory cell filtration was observed;in the platelet-rich plasma group,fiber breakage,reduced collagen fibers and inflammatory cell filtration were obviously observed;in the model control group,there were no intact tendon fibers,and inflammatory cell filtration was clearly visible.(3) The expression of matrix metalloproteinase 1:Compared with the blank control group,the expression of matrix metalloproteinase 1 was significantly higher in the other groups except the combination group (P ＜ 0.05).There was no significant difference in the expression of matrix metalloproteinase 1 between the combination group and blank control group (P ＞ 0.05).To conclude,the combination of platelet-rich plasma and tendon stem cells can inhibit the vicious cycle of degeneration of collagen and extracellular matrix,reduce the expression of matrix metalloproteinase 1 in tenocytes,and delay inflammation responses and degeneration due to tendinopathy.

Adult ; Aged ; Aged, 80 and over ; Carcinoma in Situ ; virology ; Carcinoma, Squamous Cell ; virology ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Microarray Analysis ; methods ; Middle Aged ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; diagnosis ; Paraffin Embedding ; Polymerase Chain Reaction ; methods ; Uterine Cervical Neoplasms ; virology

Tumor angiogenesis provides adequate oxygen and nutrition for tumor development and supports tumor growth and metastasis. Stromal cell derived factor 1 (SDF-1) and its receptor C-X-C motif chemokine receptor 4 (CXCR4) in pancreatic cancer microenvironment are involved in tumor growth such as promoting tumor cell proliferation, migration, and angiogenesis. In this study, anti-CXCR4 nanobody (CXCR4 Nb) and anti-programmed cell death ligand 1 (PD-L1) &CXCR4 bispecific nanobody (PX4 BsNb) were expressed in Escherichia coli system and purified by nickel column affinity chromatography. We investigated the anti-angiogenesis activity and mechanism of CXCR4 Nb by in vivo and in vitro experiments. Ethical approval was obtained for collection of human peripheral blood mononuclear cell (hPBMC) samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University. The results showed that CXCR4 Nb at 0.1 μmol·L^-1 could effectively inhibit the proliferation and migration of human umbilical vein endothelial cells (HUVEC) promoted by pancreatic stellate cells in vitro. CXCR4 Nb and PX4 BsNb at 0.3 mg·kg^-1 obviously decreased tumor angiogenesis and inhibited the tumor growth in NOD/SCID mice, the inhibitory rates were 28.8% and 36.1%, respectively. CXCR4 Nb significantly inhibited tumor growth and angiogenesis with great safety, which provides support for application of CXCR4 Nb and anti-angiogenesis therapy of pancreatic cancer.

OBJECTIVETo compare the efficacy and safety between cryoablation (Cryo) and radiofrequency (RF) ablation for treating patients with atrioventricular nodal reentrant tachycardia (AVNRT).

METHODSPatients with AVNRT (n = 304) were divided into Cryo group (n = 67) and RF group (n = 237). The procedure success rate, complete slow pathway block rate, atrioventricular block rate and relapse rate were compared between two groups.

RESULTSThere was no statistically difference between 2 groups in the success rate (Cryo group 98.5% vs RF group 97.0%, P = 0.820), complete slow pathway block rate (Cryo group 98.5% vs RF group 91.6%, P = 0.088), atrioventricular block rate (Cryo group 0 vs RF group 2.5%, P = 0.413), relapse rate (Cryo group 0 vs RF group 1.7%, P = 0.643). But Cryo group had more advantage than RF group.

CONCLUSIONEfficacy and safety were comparable between cryoablation and radiofrequency ablation for treating patients with AVNRT.

Adolescent ; Adult ; Aged ; Catheter Ablation ; methods ; Child ; Cryosurgery ; methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tachycardia, Atrioventricular Nodal Reentry ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the changes in natural killer (NK) cell count in the peripheral blood of asthmatic patients.

METHODSThe number of NK cells in the peripheral blood was determined with flow cytometry in 63 asthmatic patients with acute episodes, 65 patients with stable asthma and 62 healthy nonatopic subjects.

RESULTSA significant decrease in NK cell number was noted in asthmatic patients during acute exacerbation [(13.9-/+9.4) %] in comparison with patients with stable asthma [(22.5-/+12.3) %] and healthy subjects [(19.6-/+10.1)%] (P<0.05), and the NK cell number showed no significant difference between the latter two groups (P>0.05).

CONCLUSIONNK cell number is reduced in acute exacerbation of asthma, suggesting its important role in the asthmatic process.

Adult ; Asthma ; blood ; immunology ; Cell Count ; methods ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural ; cytology ; immunology ; Male ; Middle Aged

OBJECTIVETo explore the molecular mechanism via which the chemotherapeutic drug hydroxyurea (HU) enhances K562 cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

METHODSChronic myelogenous leukemia-derived K562 and SVT-35 cells were treated with recombinant soluble TRAIL (rsTRAIL) alone or combined with HU for a time course, and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl-2H-tetrazolium-phenazine methosulphate assay. Western blot was performed to analyze the activation of apoptosis-related protein kinases and the expression of apoptosis inhibitor molecules.

RESULTSThe survival rates of SVT-35 and K562 cells treated with 1 μg/ml rsTRAIL for 24 hours were 32% and 93%, respectively. HU significantly increased the sensitivity of K562 cells to rsTRAIL cytotoxicity. Combination of rsTRAIL and HU resulted in the phosphorylation of rat sarcoma (RAS), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase and in the significant reduction of apoptosis-inhibited molecule Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 in K562 cells.

CONCLUSIONSHU enhanced K562 cell sensitivity to rsTRAIL is mediated by Ras-MEK-ERK signaling pathway. Expression of antiapoptotic proteins cellular Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 is also down-regulated during this process. These results may through light on the therapeutic study of human chronic myelogenous leukemia.

Apoptosis ; drug effects ; physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; metabolism ; Humans ; Hydroxyurea ; pharmacology ; Inhibitor of Apoptosis Proteins ; metabolism ; K562 Cells ; MAP Kinase Signaling System ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology