Biofilms

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

OBJECTIVETo discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction.

METHODWistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3β mRNA levels.by fluorescent quantitation PCR analysis and β-catenin protein level by Western blotting.

RESULTBeing induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher β-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower β-catenin protein expression level (P < 0.01) than the normal control group.

CONCLUSIONUp-regulated β-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the β-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.

Animals ; Axin Protein ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Esophageal Diseases ; drug therapy ; genetics ; metabolism ; pathology ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Male ; Necrosis ; Nitrosamines ; adverse effects ; Proteins ; genetics ; metabolism ; Rats ; Rats, Wistar ; Wnt Proteins ; genetics ; metabolism ; Wnt Signaling Pathway ; drug effects

Background Surgery is regarded as the most effective treatment to relieve pain and reduce complications in chronic pancreatitis (CP).Two major strategies exist:duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD).Many studies suggest that DPPHR offers advantages during surgery and in the short-term; however,the long-term effects have not been thoroughly investigated.We analyzed the long-term outcomes of DPPHR and PD,over follow-up times of at least 1 year,to determine the optimal surgical treatment for CP.Methods We systemically reviewed all CP surgical treatment reports,and only included randomized controlled trials (RCT) comparing DPPHR and PD,excluding unqualified studies using several pre-specified criteria.When multiple publications of a single trial were found,the most comprehensive current data were selected.Characteristics of the study populations and long-term postoperative outcome parameters were collected.The quality of the studies and data was analyzed using RevMan 4.2 software.Results Five trials were qualified for meta-analysis,with 261 participants in total (114 in the DPPHR group and 147 in the PD group).There were no significant differences in the age,gender,or indications for surgery of each group.At the mean of 5.7-year (1-14 years) follow-up examination,DPPHR and PD resulted in equally effective pain relief,exocrine and endocrine function,and similar mortality rates (P ＞0.05); however,DPPHR patients had improved global quality of life and weight gain,and reduced diarrhea and fatigue (P ＜0.05).Conclusion DPPHR and PD result in equal pain relief,mortality,and pancreatic function; however,DPPHR provides superior long-term outcomes.

Child ; Child, Preschool ; Female ; Flow Cytometry ; methods ; Humans ; Infant ; Male ; Thrombasthenia ; classification ; diagnosis

Twelve flavonoids were isolated from an ethanol extract of Machilus wangchiana by a combination of various chromatographic techniques including column chromatography over silica gel and Sephadex LH-20 and reversed-phase flash chromatography and HPLC. Their structures were identified by spectroscopic data analysis (IR, MS, and NMR) as (+)-catechin (1), (-)-epicatechin (2), 3'-O-methyl-(+)-catechin (3), 3'-O-methyl-(-)-epicatechin (4), 3, 5, 7, 2', 5'-pentahydroxy flavan (5), (-)-naringenin (6), (-)-eriodictyol (7), (-)-liquiritigenin (8), (2R,3R)-(+)-dihydrokaempferol (9), (2R,3S)-(-)-dihydro- kaempferol (10), (2R, 3R)-(+)-taxifolin (11), and quercetin (12). Compounds 1-10 are isolated from the genus Machilus for the first time.
Drugs, Chinese Herbal ; chemistry ; Flavonoids ; chemistry ; Lauraceae ; chemistry ; Mass Spectrometry ; Molecular Structure ; Plant Roots ; chemistry

Apoptosis ; Colonic Neoplasms ; metabolism ; pathology ; HT29 Cells ; Humans ; Insulin-Like Growth Factor Binding Proteins ; metabolism

Objective To investigate the differences on lymphatic vessel density (LVD) among esophageal adenocarcinoma (EAC),esophageal squamous cell carcinoma (ESCC) and normal esophageal tissues,and analyze the clinical significance.Methods Twenty samples of EAC,24 samples of ESCC and 20 cases of normal esophageal tissues were obtained at the Affiliated Hospital of North Sichuan Medical College from January 2004 to January 2011.D2-40 was used for immunostaining of lymphatic vessels in EAC,and antibodies of D2-40 and Ki-67 were used together to detect proliferation of lymphatic vessels.The differences in the LVD among EAC,ESCC and normal esophageal tissues were analyzed.All data were analyzed using the analysis of variance or t test.Results D2-40 staining could identify the lymphatic vessels,and antibodies of D2-40 and Ki-67 could detect the proliferation of lymphatic vessels.The LVD of EAC,ESCC and normal esophageal tissues were (3.3 ± 1.7)/0.17 mm2,(4.6 ± 1.2)/0.17 mm2 and (3.8 ± 1.2)/0.17 mm2,respectively,with significant differences (F =5.44,P ＜0.05).The LVD of EAC was significantly lower than that of ESCC (t =3.074,P ＜ 0.05),while there was no significant difference in the LVD between the EAC and normal esophageal tissues (t =-1.022,P ＞ 0.05).There were significant differences in the LVD between the ESCC and normal esophageal tissues (t =2.395,P ＜ 0.05).There were significant differences in the LVD between EAC patients with deglutition discomfort and those with pain (t =3.092,P ＜ 0.05).There were significant differences in the LVD between EAC patients with course ＜6 months and those with course≥6 months (t =3.092,P ＜ 0.05).No statistical difference in clinicopathological parameters including gender,age,site of lesion,tumor diameter,pathological morphology,T stage,N stage,G stage,TNM clinical stage and lymph node metastasis were detected (t ＝ 1.130,1.020,F =0.082,t =0.799,F =0.692,t =0.694,1.820,0.353,0.969,0.969,P ＞ 0.05).Conclusions The LVD of EAC is lower than that of ESCC,but is similar to that of normal esophageal tissues.The LVD of EAC is correlated with the symptoms and course of patients.

This study was aimed to observe the natural history and evolution of cervical spondylotic myelopa-thy , explore development law of the disease incidence in order to improve the understanding of cervical spondylotic myelopathy and provide a theoretical basis for Chinese medicine treatment . Complete clinical data of 80 cervical spondylotic myelopathy cases were collected from March 1998 to July 2007 in special and ex-pert practice of Prof . Shi's out-patient department . Chinese medicine for q i-blood regulation was given in the treatment . Related measuring scales were designed . More than two-month follow-up was given through means of returning visit, telephone calls and letter inquiries. Changes of clinical symptoms, and scores of different types of evaluations were observed . The SPSS software was used in the data analysis of results from measuring scales for the objective evaluation . The results showed that there were statistical differences on the 40-score and JOA total score between initial visiting and first time follow-up ( P < 0 . 05 ) . It suggested that through Chinese medicine qi-blood regulation treatment, the scores on spinal cord function were increased compared with the previous visiting . For patients who continued long-term Chinese medicine q i-blood regulation treat-ment, there were statistical differences on the 40-score and JOA total score between the first-time follow-up and second-time follow-up ( P < 0 . 05 ) . It suggested that through continued long-term Chinese medicine q i-blood regulation treatment , the scores on spinal cord function were increased compared with the previous visit-ing . In this group of patients , there were no statistical differences on the 40-score and JOA total score be-tween the patient's initial visiting , first time follow-up , and the first-time follow-up and second-time follow-up . The scores on spinal cord function suggested that there was no obvious difference on the relieving degree between the first-time follow-up and second-time follow-up . For patients who were unable to continue the Chinese medicine qi-blood regulation treatment, no matter if it was full score on the spinal cord function in the first-time follow-up , there were statistical differences on the 40-score and JOA total score between the first-time and second-time follow-up . It suggested that the disease became worse when patients were unable to continue the Chinese medicine qi-blood regulation treatment. It was concluded that Chinese medicine qi-blood regulation treatment for cervical spondylotic myelopathy has a significant effect in both short-term and long-term treatment with steady effectiveness. Patients who continue the Chinese medicine qi-blood regulation treatment not only can prevent disease recurrence , but also can promote further relieving of disease condition .

From an ethanol extract of Euphorbia micractina roots, seven steroids fifteen aromatic derivatives were isolated by a combination of various chromatographic techniques, including column chromatography over macroporous resin, silica gel, and Sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as stigamast-5-ene-3beta, 7alpha-diol(1), stigamast-5-ene-3beta,7beta-diol(2), stigmast-5-en-3beta-ol-7-one(3), stigmast-4-en-6beta-ol-3-one(4), stigmast-1, 4-dien-3-one(5), stigmast-3,6-dione(6), beta-sitosterol(7), scopoletin(8), aesculetin(9), 6-hydroxy-5,7-dimethoxycoumarin(10), quercetin(11), 3,3', 4'-tri-O-methylellagic acid(12), p-hydroxyphenylethyl anisate(13), m-hydroxyphenylethyl alcohol(14), (E)-cinnamic acid(15), (E)-ferulic acid(16), 3,4-dihydroxybenzoic acid(17), vanillic acid(18), p-hydroxybenzoic acid(19), ethyl 3,4-dihydroxybenzoate (20), ethyl gallate(21), and methyl gallate(22). These compounds were obtained from this plant for the first time.
Drugs, Chinese Herbal ; chemistry ; Euphorbia ; chemistry ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Steroids ; chemistry