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OBJECTIVE@#To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese.@*METHODS@#Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells.@*RESULTS@#Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC50) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L.@*CONCLUSION@#This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.
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Objective To probe the new mechanism of simvastatin on high-fat diet-induced kidney dam-age. Methods Female SD rats were subjected to a standard control diet(SCD)or high-fat diet(HFD)for 20 weeks,then the HFD group was randomly divided into HFD group and HFD group with simvastatin treatment (HFD+ST,10mg·kg-1·d-1 )for another 8 weeks. The expression of adiponectin,adiponectin receptors R1 and R2, Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK),peroxisome proliferator-activated receptorα(PPARα),glucose regulated protein 78(GRP78)and GADD153(CHOP)in kidney were assessed respective-ly. Results Body weight and serum lipid levels in HFD group significantly increased ,expression of adiponectin and its receptors significantly down-regulated. Phosphorylation of AMPKα and PPARα expression decreased,and expression of GRP78 and CHOP up-regulated significantly. Above indexes in simvastatin treatment groups improved significantly. Conclusion Simvastatin can improve high-fat induced kidney damages ,probably by increasing expression of adiponectin and its receptors ,decreasing endoplasmic reticulum stress.
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Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
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BACKGROUND:Recent studies found that some factors play important role in the process of denervated muscle atrophy, especial y the feak-headbox transcription factor, is the key element to regulate the denervated muscle atrophy. OBJECTIVE:To investigate the effect of RNA interference on inhibiting feak-headbox 3a gene expression in vitro. METHODS:The myoblast cel line L6 were cultured in the 6-wel cel culture plates, then pEGFP-N1 and smal interfering RNA recombinant plasmid with the same ratio was transfected under the Lipofectamine2000 mediation to optimize the transfection efficiency of the detection system;2μg smal interfering RNA recombinant plasmid of feak-headbox 3a gene were transfected with myoblast cel line L6 for 48 and 72 hours. RESULTS AND CONCLUSION:At 48 hours after pEGFP-N1 and siRNA recombinant plasmid transfection, a large number of bright green fluorescent displayed under fluorescence microscope with higher transfection efficiency. Real-time quantitative PCR analysis showed that there were significant differences in the sequences of feak-headbox 3a-Ⅰ, feak-headbox 3a-Ⅱ, feak-headbox 3a-Ⅲ, feak-headbox 3a-Ⅳ on feak-headbox 3a mRNA when compared with the control group at 48 and 72 hours after trasfection (Phours after transfection when compared with that at 48 hours after transfection. Western Blot gray analysis showed that there were significant differences in sequences of feak-headbox 3a-Ⅰ, feak-headbox 3a-Ⅱ, feak-headbox 3a-Ⅲ, feak-headbox 3a-Ⅳ on feak-headbox 3a mRNA when compared with the control group at 48 and 72 hours after trasfection (Psignificantly inhibit the fork-head transcription factor feak-headbox 3a gene expression, and the inhibition effect of feak-headbox 3a gene smal interfering RNA recombinant plasmid transfected with the sequence on the mRNA and protein level of feak-headbox 3a is not clear, which can provide new idea for the gene therapy of RNA mediated denervated skeletal muscle atrophy.
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PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
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OBJECTIVE: To summarize the reconstruction exp erience of the electrical injuries in emergency. METHODS: All 309 wounds in 105 patients who suffered from elect rical injuries were reviewed during a 10 year period from Jan. 1st 1986 to Dec. 31st, 1996. Treatment method, patient data and results wer e compared and analyzed. A comprehensive urgent reconstruction alternative used in all cases included the followings, 1) debriding the wound in emergency, 2) preserving the vital tissues as much as possible, even devitalized tissues or loca l necrosis, 3) transplanting these vital tissues during the first surgery if the functional reconstruction required, 4) nourishing the wound bed by tissue flaps covering with rich blood supply, 5) improving flap survival by continuous irrig ation for 24-720 hours beneath the flaps with a compound medicine after surgery. RESULTS: Satisfactory results were obtained with the extremity loss ratio of less than 7% in this group compared with 42.5% which was 10 ye ars before 1984 in the same hospital. CONCLUSIONS: This urgent comprehensive reconstruction alternati ve is an effective and workable method for reducing extremity loss of electrical injuries.
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Objective Introducing a technique of quantitative eschar shaving with great sheet of epidermal grafting for deep Ⅱdegree burns in hands.Method 148 hands from 112 patients were treated with this methods.From Jan.2001 to Jane 2004,patients who suffered from deep Ⅱdegree burn injuries was quantitatively eschar shaving using electrical or air power dermatome which was fixed at scale mark from 0.012 inc 、0.016 inc to 0.02inc(from 0.3mm 、0.4mm to 0.5mm) according to the burn injury extents,the wounds were divided into three groups just depends on the injury extents,also the wounds was covered with the different thickness of great sheet of epidermal grafting,which was obtained using the electric or air dermatomes.Results There were 148 hands of 112 cases were treated with this technique within 2h.to 72h after injury.The scar thickness was ranged from 0.4mm to 0.8mm,the function of these hands was good,and the shape of hands looks good.Conclusion Good results was obtained with this methods,the wounds covered with the large sheet of epidermal grafting harvested by the quantitative eschar shaving is recovered uneventful.The thickness of the grafting was according to the increasing skin thickness after burns.