The secondary metabolites from a mutant 3d10-01 derived from Penicilliumchrysogenum S-3-25 by diethyl sulfate mutagenesis / 国际药学研究杂志

Objective To investigate the secondary metabolites from diethyl sulfate(DES)mutant 3d10-01 derived from Peni-cillium chrysogenum S-3-25. Methods The secondary metabolites were isolated by multiple separation techniques,such as silica gel,Sephadex LH-20 column chromatography and HPLC. The structures of the compounds were determined by ESI-MS and NMR spectroscopic data. The antitumor activity was assayed by the MTT method. HPLC-UV analysis was used to determine if compounds 1-7 were newly produced by the mutant. Results Seven secondary metabolites,including methyl 2,4-dihydroxy-3,5,6-trimethylbenzo-ate(1),6-hydroxymethyl-2,2-dimethylchromanone(2),regiolone(3),(3S,4S)-3,4-dihydro-3,4,8-trihydroxy(2H)naphthalenone (4),cerebroside C(5),cerebroside D(6)and dankasterone A(7),were isolated from the fermentation products of the mutant 3d10-01. Compounds 1,4 and 7 showed strong inhibitory effects on the five tested cell lines,but 2,3 and 6 only exhibited the proliferation of HL-60 cells to some extent. Compounds 1-4 and 7 were newly produced by the mutant 3d10-01. Conclusion Compounds 1-7 are firstly isolated from P. chrysogenum. The inhibitory effects on certain tested antitumor cell lines of compounds 1-4,6 and 7 are report-ed for the first time.

Pteridic acid hydrate and pteridic acid C produced by StreStreptomyces pseudoverticillus YN17707 induce cell cycle arrest / 中国天然药物

The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on tsFT210 cells. Compounds were isolated through various chromatographic methods and elucidated by spectroscopic analyses. Flow cytometry was used to evaluate the cell cycle inhibitory activities of the fractions and compounds. Two compounds were obtained and identified as pteridic acid hydrate (1) and pteridic acid C (2), which arrested the tsFT210 cells at the G0/G1 phase with the MIC values being 32.8 and 68.9 μmol·L(-1), respectively. These results provide a basis for future development of Compounds 1 and 2 as novel cell cycle inhibitors for cancer therapy.

Drinking-water type fluorosis treated with acupuncture of reinforcing kidney and activating spleen: a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To observe the impacts of acupuncture of reinforcing kidney and activating spleen on the excretion of urinary fluoride and pain of the patients with drinking-water type fluorosis.</p><p><b>METHODS</b>The randomized controlled and single-blind trial was adopted. Seventy-two cases were randomized into an observation group and a control group, 36 cases in each one. In the observation group, acupuncture was applied at Pishu (BL 20), Shenshu (BL 23), Guanyuan (CV 4), Zusanli (ST 36), etc. , three treatments a week. In the control group, the Calcium Carbonate D3 tablets were prescribed for oral administration, 600 mg each time, twice a day. The duration of treatment was 2 months. The changes of the content of urinary fluoride and pain score (by VAS) before and after treatment between two groups were compared.</p><p><b>RESULTS</b>The urinary fluoride excretion was increased obviously after treatment in the observation group (P < 0.01), which was superior apparently to that in the control group [(11.06 +/- 4.54) mg/L vs. (8.30 +/- 4.14) mg/L, P < 0.05]. After treatment, VAS score was reduced significantly in either group (both P < 0.01). The result in the observation group was lower remarkably than that in the control group (1.93 +/- 1.30 vs. 3.47 +/- 2.29, P < 0.01).</p><p><b>CONCLUSION</b>Acupuncture achieves the significant efficacy on the promotion of urinary fluoride excretion and pain relieving of the patients with drinking-water type fluorosis in light of reinforcing kidney and activating spleen, which is superior to the oral administration of the calcium carbonate D3 tablets.</p>

Screening for bioactive mutants with antitumor activity from an actinomycetic wild-type strain without antitumor activity by antibiotic-resistant mutation technique and by coupled with chemical mutagen-induced mutation / 军事医学科学院院刊

Objective To obtain antibiotic-resistant mutants producing metabolites with antitumor activity from wild-type actinomycete strains without antitumor activity. Methods An actinomycete strain L35-1 was used as an initial strain for obtaining antibiotic-resistant mutants, which is a marine-derived wild-type strain without antitumor activity with an inhibition rate of 2.8% at the 1000 μg/ml of high sample concentration on K562 cells. The antibiotic-resistant mutants both from auto-mutagenesis and chemical mutagen-induced mutagenesis were selected by single colony isolation on antibiotic-containing plates according to the method for obtaining drug-resistant mutants in ribosome engineering. The antitumor activity was assayed by the MTT method using K562 cells for the mutants with aqueous acetone extracts of the whole broth of their fermentation.Results A total of 114 neomycin-resistant (ner) and 68 streptomycin-resistant (str) mutants, all from auto-mutagenesis, was obtained on drug-containing plates. Among them, the 7 ner and 3 str mutants appeared to be bioactive with an inhibition rate above 20% at the 100 μg/ml sample concentration on K562 cells. On the other hand, 41 str and 32 ner mutants from DES-induced mutagenesis and 46 ner mutants from NTG-induced mutagenesis were obtained by mutagen-induced mutation coupled with the single colony isolation on antibiotic-containing plates, among which, one str mutant from DES-induced mutagenesis and one ner mutant from NTG-induced mutagenesis were bioactive with an inhibition rate over 20% at the 100 μg/ml sample concentration on K562 cells. Conclusions The present result has revealed that the wild-type actinomycete strains without bioactivity might become a great source initial strains to obtain bioactive mutants by drug-resistant mutation technique.

A new approach for exploiting microbial new strain resources for drug screening / 国际药学研究杂志

Generally absolute majority of wild-type microbial strains do not produce bioactive metabolites, resulting in large numbers of so-called 'useless strains' stocked or destroyed. These strains, however, would become a great source of bioactive meabolites if their secondary metabolism could be altered to produce diverse metabolites. We have therefore undertaken a research work on exploiting microbial new strain resources for drug screening by altering secondary metabolism of the 'useless strains' to discover bioactive metabolites. A considerable progress with expectant advantage desired has been made in the studies on marine-derived actinomycetic and fungal strains. This paper summarizes our research results including several new developments in brief.

Observation on therapeutic effect of Hwato never and muscle stimulator on peripheral facial paralysis / 中国针灸

<p><b>OBJECTIVE</b>To observe the therapeutic effect of Hwato never and muscle stimulator on peripheral facial paralysis.</p><p><b>METHODS</b>Eighty-seven cases of peripheral facial paralysis were randomly divided into a Hwato never and muscle stimulator observation group (n=44) and a G 6805 electronic stimulator control group (n=43). The same acupoints, Hegu (LI 4), Sanyinjiao (SP 6), Taichong (LR 3) and local acupoints on the affected side were selected in the two groups. The therapeutic effects were compared between the two groups.</p><p><b>RESULTS</b>Although the total effective rates were both 100.0% in the two groups, the cured rate was 90.9% in the observation group and 62.8% in the control group with a significant difference between the two groups (P < 0.05). There were no adverse effects in the two groups.</p><p><b>CONCLUSION</b>The cured rate of Hwato never and muscle stimulator on peripheral facial paralysis is superior to that of G 6805 electronic stimulator.</p>

On the important role of Siguan points in treatment of chronic fatigue syndrome / 中国针灸

<p><b>OBJECTIVE</b>To probe into the role of Siguan points in treatment of chronic fatigue syndrome.</p><p><b>METHODS</b>Based on diagnosis, pathogenesis and etiology of chronic fatigue syndrome in TCM, the role of Siguan points in treatment of chronic fatigue syndrome were induced by means of relative literatures of Siguan points in recent 10 years from 3 aspects.</p><p><b>CONCLUSION</b>Acupuncture at Siguan as main points has a better therapeutic effect on chronic fatigue syndrome.</p>

On functional area of Back-shu based on relationship between Back-shu points and Jiaji points / 中国针灸

<p><b>OBJECTIVE</b>To prove the existence of functional area of Back-shu and provide a new thinking for clinical practice.</p><p><b>METHODS</b>The consistency between the Back-shu points and Jiaji points at the same level of spinal column was discussed from the origin and development, mechanisms and clinical application of Back-shu and Jiaji points.</p><p><b>CONCLUSION</b>The points at the same level of spinal column has same origin of development, mechanisms and clinical functions, so as to prove the existence of functional area of Back-shu.</p>

Vitexicarpin, a flavonoid from Vitex trifolia L., induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway / 药学学报

<p><b>AIM</b>To investigate the inhibitory effect of vitexicarpin on the proliferation of human cancer cells and its mechanism of action.</p><p><b>METHODS</b>The inhibitory effect of vitexicarpin on the proliferation of human cancer cells was evaluated by the SRB method and its apoptosis-inducing effect was demonstrated by morphological observation under light microscope, flow cytometric analysis and agarose gel electrophoresis. The proteins related to apoptosis were examined by Western blotting analysis.</p><p><b>RESULTS</b>Vitexicarpin significantly inhibited the proliferation of human cancer cells, A2780, HCT-15, HT-1080 and K562, with the IC50 values of (19.1 +/- 2.4) micromol x L(-1) for A2780(48 h), (0.66 +/- 0.10) micromol x L(-1) for HCT-15(48 h), (0.44 +/- 0.06) micromol x L(-1) for HT-1080 (48 h) and (0.28 +/- 0.14) micromol x L(-1) for K562 (24 h). The cells treated with vitexicarpin showed characteristic morphology typical for apoptosis and gave dose-dependent sub-G0/G1 peak in the flow cytometric analysis and DNA ladder on agarose gel electrophoresis. In Western blotting analysis, the cleavage of PARP and caspase-3, the release of cytochrome c from mitochondria into the cytosol, the decrease of Bcl-2 expression level, and the down-regulation of the ratio of Bcl-2/Bax expression level were examined in the K562 cells treated with vitexicarpin.</p><p><b>CONCLUSION</b>Vitexicarpin induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway.</p>

Apoptosis-inducing effect of carbazole alkaloid (HY-1) in human erythroleukemia K562 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate apoptosis-inducing effect and its mechanisms of HY-1, a carbazole alkaloid, on human erythroleukemia K562 cells.</p><p><b>METHODS</b>Cell proliferation was detected by sulforhodamine B (SRB) assay after treated with HY-1 at indicated doses. Cell cycle analysis was performed by flow cytometry, mitochondria membrane voltage change was assessed by rhodamine 123 staining, annexin V-PI apoptosis detecting kit and DNA agarose gel electrophoresis were used to identify apoptosis-inducing effect of HY-1. The alterations of apoptosis-relating proteins were detected by Western blot.</p><p><b>RESULTS</b>The IC(50) of HY-1 in K562 cells was (29.05 +/- 0.90) micromol/L by SRB assay. HY-1 had significant apoptotic inducing effect on K562 cells in a dose- and time-dependent manner as verified by appearance of Sub-G(1) peak on histogram of flow cytometry analysis, reduction of mitochondria membrane voltage, appearance of double positive cell group in Annexin V-PI apoptosis detecting test, and remarkable DNA ladder. The expression of cytosolic cytochrome c was apparently increased. Pro-caspase-9, pro-caspase-3 and PARP were all cleaved to active segments. There was no change in the expression of caspase-8.</p><p><b>CONCLUSION</b>HY-1 exerts its anticancer activity through triggering apoptosis of K562 cells by mitochondria-activating pathways.</p>