Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

10.3969/j.issn.2095-4344.2013.25.023

An investigation on the chemical constituents of the 90% EtOH extract of Perovskia atriplicifolia led to the isolation of fifteen compounds from the EtOAc fraction. Based on the detailed spectral analysis (MS, 1D and 2D NMR), as well as comparison with the literatures, the structures of compounds 1-15 were determined as cirsimaritin (1), salvigenin (2), syringaldehyde (3), vinyl caffeate (4), 2α, 3α-dihydroxyolean-12-en-28-oicacid (5), 2α, 3α-dihydroxyurs-12-en-28-oicacid (6), niga-ichigoside F1 (2α, 3β, 19α, 23- tetrahydroxyurs - 12-en-28-oicacid- O-β-D- glucopyranoside, 7), sericoside (8), 4-epi-niga-ichigoside F1 (2α, 3β, 19α, 24-tetrahydroxyurs-12-en-28-oicacid O-β-D-glucopyranoside, 9), 2α, 3β, 24-trihydroxyolean-12-en-28-oicacid O-β-D-glucopyranosyl-(1 --> 2) - β-D-glucopyranoside (10), pruvuloside A (11), asteryunnanoside A [2α, 3β, 23-trihydroxyolean-12-en-28-oicacid O-β-D-glucopyranosyl-(1 --> 2)-β- D- glucopyranoside,12], rosmarinic acid methyl ester (13), β-sitosterol (14), and daucosterol (15), respectively. Compounds 1-13 were isolated from the Perovskia genus for the first time. All the compounds were obtained from P. atriplicifolia for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Lamiaceae ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization

BACKGROUNDSmall acoustic neuromas seldom result in typical vestibular symptoms, despite the tumor arising from the vestibular nerve. In this study, we have shown that abnormal gait in eleven patients with small acoustic neuroma could be detected in gait analysis by the use of tactile sensor. Patients displayed no oculomotor abnormality and had tumors less than 10 mm from the porus acoustics.

METHODSGait related parameters including the coefficients of variations (CV) of stance, swing, double support, area ratio of trajectories of center of force (TCOF), in addition to the foot pressure difference between both feet, were used for assessment of gait.

RESULTSThe CV of swing and the area ratio of TCOF were greater in patients than those in the control group (P < 0.05). The values of these two parameters became greater under an eyes closed condition compared to eyes open (P < 0.05) in the patient group.

CONCLUSIONThese results indicate that gait analysis may be helpful to assess vestibulospinal function of patients with small acoustic neuroma, the slight vestibular deficits of which can not be detected by visual observation.

Adult ; Aged ; Female ; Gait Disorders, Neurologic ; diagnosis ; etiology ; Humans ; Male ; Middle Aged ; Neuroma, Acoustic ; physiopathology

OBJECTIVE: By detecting the myelin structure in acoustic tumor tissues, the cell origin and state of acoustic tumor tissues were investigated. METHOD: Immunofluorescence labeling, immunoblot analysis and electron microscopic study were performed to identify myelin structure and myelin protein in acoustic tumor tissues. RESULT: In this work, we found some early stage of myelin forming in acoustic tumor tissues, but there were no axon nor compact myelin formed and the myelin basic protein whose expression indicates the beginning of myelination was negative detected. We also found that the cell of acoustic tumor express p75,a marker for immature Schwann cells and mature non-myelin-forming Schwann cells. CONCLUSION The date shown in this experiment indicates that the cell of acoustic tumor is in a remyelinating state.
Humans ; Microscopy, Electron ; Myelin Sheath ; pathology ; ultrastructure ; Neuroma, Acoustic ; pathology ; Schwann Cells ; pathology

OBJECTIVETo evaluate technique aspects of video-assisted thoracoscopic lobectomy for benign diseases.

METHODSRetrospective review of 24 patients with benign pulmonary disease underwent thoracoscopic lobectomy from September 2006 to September 2008. One patient had bilateral bronchiectasis received concurrent bilateral lobectomy. The patients included 11 males and 13 females with mean age of 49.0 years. Fifteen cases were diagnosed as benign diseases preoperatively consisted 10 bronchiectasis as the primary indication. The other 9 cases were pulmonary nodules pathologic diagnosed intra-operatively. Inflammation changes including dense plural adhesions, pulmonary artery adhesions and calcified lymph nodes were managed endoscopically.

RESULTSAll 25 thoracoscopic procedures were completely with no conversion to thoracotomy. The mean operation time was (163 +/- 52) min, blood loss was (163 +/- 130) ml. There was no hospital death or major morbidity. Postoperative drainage was (5.8 +/- 2.8) d. No long-term complications were noticed during a mean follow-up of 7.3 months.

CONCLUSIONChronic inflammation induced adhesions is the key limiting factor for thoracoscopic lobectomy for benign diseases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Lung Diseases ; surgery ; Male ; Middle Aged ; Pneumonectomy ; methods ; Retrospective Studies ; Thoracoscopy ; Young Adult

OBJECTIVETo study the inhibitory effect of mutant K-ras gene depletion by small interfering RNA on the growth of lung cancer cell line-H441 cells in vitro and in vivo.

METHODSOne pair of 63 bp reverse repeated sequence targeting mutant K-ras(V12) mRNA spaced by 9 bp nucleotide were synthesized and inserted into plasmid pSilencer3.1 eukaryotic expression vector. After transient and stable transfection into H441 cells, the mutant K-ras mRNA and protein level were measured by RT-PCR and Western blotting, and the H441 cells proliferation was measured by MTT method, and the apoptosis rate was detected by flow-cytometry. H441 cells treated with pSilencer3.1-K-ras(V12) were transplanted subcutaneously in nude mice and their tumorigenesis ability was observed.

RESULTSThe recombinant plasmid pSilencer3.1-K-ras(V12) was successfully constructed by sequencing. The introduction of pSilencer3.1-K-ras(V12) was showed to efficiently and specifically inhibit the expression of K-ras(V12) gene according to the results of RT-PCR and Western blotting (P < 0.01, as compared with controls). The inhibitory effect on cell proliferation was confirmed by MTT test (P < 0.05, as compared with controls). Apoptosis rate of H441 cells treated with pSilencer3.1-K-ras(V12) was significantly higher than that of the control cells (P < 0.01). The test in vivo showed that downregulation of K-ras(V12) expression in H441 cells apparently affected their ability to form tumors in nude mice.

CONCLUSIONSsiRNA targeting mutant K-ras mRNA can specifically suppress the expression of mutant K-ras gene in H441 cells, and therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo, it provides a new method and material to the gene therapy of lung cancer.

Adenocarcinoma ; genetics ; pathology ; therapy ; Animals ; Apoptosis ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Gene Silencing ; Genetic Therapy ; Genetic Vectors ; Humans ; Lung Neoplasms ; genetics ; pathology ; therapy ; Mice ; Mice, Nude ; Plasmids ; genetics ; Point Mutation ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Xenograft Model Antitumor Assays ; ras Proteins ; genetics ; metabolism

BACKGROUNDThe feasibility of completing a lobectomy by completely video-assisted thoracoscopic surgery (cVATS) in the management of bronchiectasis is unclear. By retrospectively comparing the outcomes from the lobectomies that used thoracotomy vs. cVATS, we determined the appropriateness of the minimally invasive cVATS approach in the management of bronchiectasis.

METHODSBetween June 2001 and October 2010, 60 patients with bronchiectasis underwent surgery, of which 56 lobectomies were performed. All lobectomies were carried out by either thoracotomy or cVATS approach. Pulmonary vessels and bronchi were manipulated by ligation or stapler in the thoracotomy group, while they were dissected by endo-cutters in the cVATS group.

RESULTSThere were 21 patients in the thoracotomy group and 35 patients in the cVATS group. Two cVATS patients (5.7%) converted. The difference in operation time, chest tube duration, lengths of hospitalization, and morbidity were not significantly different between the two groups (P > 0.05). The blood loss was less in the cVATS group (P = 0.015). A total of 52.4% and 62.9% of patients were postoperatively asymptomatic in the thoracotomy and cVATS groups respectively, and symptomatic improvement was obtained in 38.1% patients by thoracotomy vs. 31.4% patients by cVATS.

CONCLUSIONcVATS lobectomy is safe and effective for the management of bronchiectasis, especially for the patients with localized lesions.

Adult ; Bronchiectasis ; surgery ; Female ; Humans ; Male ; Middle Aged ; Thoracic Surgery, Video-Assisted ; methods

BACKGROUNDCompletely video-assisted thoracoscopic lobectomy is a reasonable treatment for early-stage non-small-cell lung cancer (NSCLC). At present, the indication for this procedure is stage Ia and Ib peripheral lung cancer (≤ 5 cm); however, for larger tumors, it remains controversial whether this surgical technique is comparable to open lobectomy. This study aimed to evaluate the safety, completeness, and efficacy of thoracoscopic lobectomy, and to compare this technique with open lobectomy for the treatment of non-small-cell lung cancer when the tumor's diameter was greater than 5 cm.

METHODSFrom May 2001 to April 2011, 802 patients underwent a lobectomy for treatment of non-small-cell lung cancer at our center. In 133 patients, the tumor was > 5 cm. There were 98 men and 35 women, median age 63 years (range: 29 - 81 years). We divided the patients into two groups, group V (completely video-assisted thoracoscopic surgery), and group T (open lobectomy), and evaluated the two groups for age, gender, tumor size, pathological type, location, duration of surgery, blood loss, lymph node dissection, pathological stage, time of drainage, hospitalization, complications, overall survival and recurrence.

RESULTSThere were 46 cases in group V and 87 cases in group T. Age, gender, tumor size, location, pathological type and stage were similar between the two groups. Group V had shorter operative duration ((186.5 ± 62.8) minutes vs. (256.7 ± 67.5) minutes, P < 0.001) and reduced bleeding ((218.5 ± 174.6) ml vs. (556.9 ± 187.2) ml, P < 0.001). There were no significant differences between the two groups in complications, lymph node dissection, time of drainage and hospitalization. The recurrence between the two groups was equivalent (2.4% vs. 3.8%, P = 0.670). The overall survival at 1, 2 and 3 years was 95.1%, 81.6% and 69.6% for group V and 88.3%, 78.8% and 64.0% for group T. Kaplan-Meier survival curves showed that there was no significant differences between the two groups (P = 0.129).

CONCLUSIONSCompletely video-assisted thoracoscopic lobectomy was similar to open lobectomy in safety, completeness, and efficacy, but had a shorter operative duration, and reduced bleeding. This is a minimally invasive procedure that is feasible for a subset of non-small-cell lung cancer patients with tumor size > 5 cm.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Pneumonectomy ; adverse effects ; methods ; Retrospective Studies ; Thoracic Surgery, Video-Assisted ; adverse effects ; methods ; Treatment Outcome

BACKGROUNDThe combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer (NSCLC). But this doublet has considerable toxicity and unfavorable tolerability, and results in poor compliance. The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC, but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting.

METHODSFrom a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m(2)) and gemcitabine (1250 mg/m(2)) between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records.

RESULTSA total of 132 patients met the criteria and were included in the study, 96 were male (72.7%) and 36 were female (27.3%). Median age was 60.5 years old, range 29 - 75 years, and 41.7% of patients were ≥ 65 years old. Overall, 68.2% patients received all four planned cycles, and the cumulative dose delivered for gemcitabine was 8333 mg (83.3% of the planned dose) and cisplatin 248 mg (82.7% of the planned dose). There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 patients (35.6%) and was the predominant hematologic toxicity. Common grade 3/4 non-hematologic toxicities were nausea/vomiting (22.0%), infection (12.3%), and febrile neutropenia (11.4%).

CONCLUSIONCisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerability compared with published data on cisplatin and vinorelbine.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Retrospective Studies