SARS coronavims is an emerging virus. A lot of animals could be infected by SARS-CoV and Himalayan palm civets, as one of important hosts, is an ideal animal model. Viral genetic factors have been implicated in the emergence of SARS-CoV, with the suggestion that this virus is a recombinant between mammalian and avian coronaviruses. However, the recombination is unlikely to explain the appearance of SARS in humans.

Mutation (substitution, deletion, insertion, etc.) in nucleotide acid causes the maximal sequence lengths of exact match (MALE) between paralogous members from a duplicate event to become shorter during evolution. In this work, MALE changes between members of 26 gene families from four representative species (Arabidopsis thaliana, Oryza sativa, Mus musculus and Homo sapiens) were investigated. Comparative study of paralogous' MALE and amino acid substitution rate (d(A)<0.5) indicated that a close relationship existed between them. The results suggested that MALE could be a sound evolutionary scale for the divergent time for paralogous genes during their early evolution. A reference table between MALE and divergent time for the four species was set up, which would be useful widely, for large-scale genome alignment and comparison. As an example, detection of large-scale duplication events of rice genome based on the table was illustrated.
Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Arabidopsis ; genetics ; Chromosome Mapping ; methods ; Conserved Sequence ; genetics ; Evolution, Molecular ; Humans ; Mice ; Molecular Sequence Data ; Oryza ; genetics ; Proteome ; genetics ; metabolism ; Sequence Alignment ; methods ; Sequence Analysis, Protein ; methods ; Sequence Homology, Amino Acid ; Species Specificity

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.
Animals ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; Carboxylic Acids ; Carcinoma, Hepatocellular ; Cell Line ; Cell Proliferation ; Drug Design ; Escherichia coli ; drug effects ; Fluoroquinolones ; chemical synthesis ; chemistry ; HL-60 Cells ; Humans ; Leukemia L1210 ; Liver Neoplasms ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Naphthyridines ; Triazines

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Cell Line, Tumor ; Fluoroquinolones ; chemistry ; Humans ; Oxadiazoles ; chemistry ; Structure-Activity Relationship

Evaluation Studies as Topic ; Humans ; Medicine, Chinese Traditional ; Publishing ; standards ; Quality Control ; Randomized Controlled Trials as Topic ; standards

Adult ; Burnout, Professional ; Female ; Humans ; Life Change Events ; Middle Aged ; Occupations ; Professional Competence ; Work ; psychology ; Young Adult

OBJECTIVETo observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis.

METHODSixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1.

RESULTAfter 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05).

CONCLUSIONDetoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.

C-Reactive Protein ; metabolism ; Carotid Artery Diseases ; blood ; drug therapy ; Crataegus ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Fallopia japonica ; chemistry ; Female ; Humans ; Male ; Matrix Metalloproteinase 1 ; blood ; Middle Aged ; Safety ; Tissue Inhibitor of Metalloproteinase-1 ; blood

Objective To study the clinical features,diagnosis and treatment of eosinophilic granuloma of bone(EGB).Methods Twelve cases(8 male and 4 female)of EGB and their medical record,imaging examinations,follow-up data were reviewed,and the lesion sites,symptom and clinical features were analyzed with reference to relative literature.Results Nine unifocal cases were found in the cervical spine(3 cases),the thoracic spine(1 case),the lumber spine(1 case),the femur(1 case),the metacarpal bones(1 case),and the ilium(2 cases).Three multifocal cases were found in the thoracic and lumber spine(1 case),in the femur,the multiple ribs,the skull,the scapula(1 case)and in the skull,the femur,the ilium(1 case).The most common presenting symptom was pain at the lesion site and restricted motion was obviously in the cervical lesion.The case of the thoracic lesions was found neurologic deficit.Osteolytic destruction was found in the radiologic examination in EGB and the periosteal reaction was found in the long bone lesions,and vertebra plana was considered as typical cha-racteristics in the spine lesion.The lesions not in the spine were diagnosed by biopsy,exclusive methods and close following-up were performed in the spine lesions.Two unifocal were healed spontaneously and three were performed with curettage with one bone grafting.Multifocal and the lesions in the spine underwent chemotherapy.All cases were followed up and no recurrence was found.Conclusions EGB is commonly solitary and not seldom in the spine.Topical pain may be chief complaint.Osteolytic image was found in the radiologic examination.Biopsy and exclusive methods combining closely follow-up were used for diagnosis.EGB is self-limited observation,so curettage or chemotherapy can be used in treatment,and prognosis is good.

BACKGROUND: Nicotine, which is a known central nervous system stimulant, appears to be the neuroprotective factor of Parkinson disease(PD). It has been reported that PD patients' symptoms such as trembling,rigor, hypokinesia are ameliorated during smoking, but its mechanism still keeps unclear.OBJECTIVE: To observe the effects of nicotine on gene expression levels of dopamine D1 and D2 receptors (D1R,D2R)in striatum of rats and analyze the possible mechanism of behavioral changes of rats induced by nicotine.DESIGN:Randomized and controlled experiment.SETTING:Institute of Neurology, Xiangya Hospital, Central South University.MATERIALS :Twenty-four SD rats aged at 10 weeks were chosen,weighing 180-200 g. Nicotine (Sigma),revert AidTM M-Mulv reverse transcriptase (MBI Fermentas,USA), polymerase chain reaction (RCR,Beckman),densitometric scanning imaging system (Stratagene Eagle Eye Ⅱ ,USA).METHODS :This experiment was carried out in the Laboratory of Institute of Neurology, Xiangya Hospital,Central South University from July 2001 to July 2002. These rats were divided into two groups: control group (n=12)and nicotine group(n=12). The level of D1 and D2 receptors on striatum of rats was estimated at the timepoint of thirty-minute after chronic nicotine administration (4 mg/kg per day s.c.), and the behavioral activities were also recorded at the same timepoint for thirty minutes. The functional behavioral activities recorded included: rearing up repeatedly, moving about, provoking, climbing, grooming, yawning, rotating, smelling and vomiting. At the fourteenth day, all rats were killed after thirty minutes of nicotine injection,the brains were dissected out and the region of striatum was separated immediately. Total RNA was extracted from striatum by RNeasy Total RNA Kit. PCR amplification was performed at special condition. For semi-quantitative analysis, 10 μ L of PCR products for each was examined by electrophoresis on 12 g/L agarose gel containing 0.5 mg/L ethidium bromide,and absorbance (A value) was quantitated by using densitometric scanning imaging system, thuse D1R,D2R mRNA expression were determined. Differences between means were analyzed with two-tailed student's t test.MAIN OUTCOME MEASURFS: Changes of locomotor activities and the gene mRNA expression levels of D1 R and D2R in the regions of striatum in rats.RESULTS: Totally 24 SD rats were involved in the final results.① Locomotor activities of rats become more active after 3-day nicotine administration and reach the top during 7-14 days.②The A value of total RNA ratio of A260/A280 ＞1.8, and the total RNA had no degradation with 12 g/L agarose gels electrophoresis. ③As expected, PCR amplification product lengths of D1R, D2R,βA were 350 bp, 399 bp, 218 bp respectively. A significant increase of 23% of D1R mRNA expression in the region of striatum detected in the nicotine group compared with that of control group (98.63±1.13 and 65.29±1.45 seperately,P ＜ 0.01), no difference was detected on the level of D2R mRNA expression in the same regions above (76.73±1.45 and 78.21±1.69 respectively ,P ＞ 0.05 ).CONCLUSION: Nicotine may induce changes of locomotor activities of rats by up-regulating D1R mRNA expression in striatum.

This study was designed to explore the RNA interference technique in inhibition of the expression of the mouse fibrinogen like protein 2 (mfgl2), which has been reported to be involved in the development a variety of diseases including fulminant viral hepatitis. A plasmid named p-mfgl2shRNA,complementary to the sequence of mfgl2 was constructed, while another short hairpin RNA (shRNA)which was a mutated form of the mfgl2shRNA sequences was used as a control. A plasmid named pEGFP-mfgl2 expressing the mfgl2-EGFP fusion protein was also constructed for the screening of the effect of p-mfgl2shRNA on mfgl2 expression. By cotransfection of p-mfgl2shRNA and pEGFP-mfgl2 or pcDNA3.1-mfgl2 expression construct into CHO cells or HeLa cells, the inhibition of mfgl2 expression by mfgl2shRNA was analyzed by direct observation through fluorescent microscopy, FACS, RT-PCR and immunohistochemistry staining. The experiments showed the significant inhibitory effect of p-mfgl2shRNA on mfgl2 expression at 48h post-transfection in both CHO and Hela cell lines with the inhibitory efficiency as high as 80.1%. The study demonstrated that the construct of p-mfgl2shRNA successfully interfered with the mfgl2 expression in vitro.